VCV000992268.1 - ClinVar

NM_004333.6(BRAF):c.2128-16delinsTCT

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_004333.6(BRAF):c.2128-16delinsTCT

Variation ID: 992268 Accession: VCV000992268.1

Type and length

Indel, 3 bp

Location

Cytogenetic: 7q34 7: 140734786 (GRCh38) [ NCBI UCSC ] 7: 140434586 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jan 7, 2021	Jan 7, 2021	Dec 22, 2020

HGVS

Nucleotide	Protein	Molecular consequence
NM_004333.6:c.2128-16delinsTCT MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_001374258.1:c.2248-16delinsTCT MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_001354609.2:c.2128-16delinsTCT		intron variant
NM_001374244.1:c.2248-16delinsTCT		intron variant
NM_001378467.1:c.2137-16delinsTCT		intron variant
NM_001378468.1:c.2127+5026delinsTCT		intron variant
NM_001378469.1:c.2062-16delinsTCT		intron variant
NM_001378470.1:c.2026-16delinsTCT		intron variant
NM_001378471.1:c.2017-16delinsTCT		intron variant
NM_001378472.1:c.1972-16delinsTCT		intron variant
NM_001378473.1:c.1972-16delinsTCT		intron variant
NM_001378474.1:c.2127+5026delinsTCT		intron variant
NM_001378475.1:c.1864-16delinsTCT		intron variant
NC_000007.14:g.140734786delinsAGA
NC_000007.13:g.140434586delinsAGA
NG_007873.3:g.194979delinsTCT
LRG_299:g.194979delinsTCT
LRG_299t1:c.2128-16delinsTCT

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000007.14:140734785:G:AGA

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

dbSNP: rs1796250484 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
BRAF		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	1249	1363

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Benign (1)	criteria provided, single submitter	Dec 22, 2020	RCV001280678.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (Dec 22, 2020)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV001467976.1 First in ClinVar: Jan 07, 2021 Last updated: Jan 07, 2021	Comment: Variant summary: BRAF c.2128-16delinsTCT alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly … (more) Variant summary: BRAF c.2128-16delinsTCT alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 159536 control chromosomes (gnomAD), however the variant is located to a highly polymorphic poly-T region, where several similar variants occur with a high allele frequency, suggesting that this variant could be a benign polymorphism. To our knowledge, no occurrence of c.2128-16delinsTCT in individuals affected with Cardiofaciocutaneous Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign. (less)

Comment:

Variant summary: BRAF c.2128-16delinsTCT alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 159536 control chromosomes (gnomAD), however the variant is located to a highly polymorphic poly-T region, where several similar variants occur with a high allele frequency, suggesting that this variant could be a benign polymorphism. To our knowledge, no occurrence of c.2128-16delinsTCT in individuals affected with Cardiofaciocutaneous Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs1796250484 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 17, 2022

ClinVar Genomic variation as it relates to human health

NM_004333.6(BRAF):c.2128-16delinsTCT

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1796250484 ...