VCV000040089.3 - ClinVar

NC_000004.12:g.98929153dup

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.

risk factor

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_000004.12:g.98929153dup

Variation ID: 40089 Accession: VCV000040089.3

Type and length

Duplication, 1 bp

Location

Cytogenetic: 4q23 4: 98929146-98929147 (GRCh38) [ NCBI UCSC ] 4: 99850297-99850298 (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	Apr 4, 2013	Oct 7, 2023	Nov 1, 2009

HGVS

Nucleotide	Protein	Molecular consequence
NC_000004.12:g.98929153dup
NC_000004.11:g.99850304dup
NG_047048.2:g.6489dup

Protein change

Other names

Canonical SPDI

NC_000004.12:98929146:GGGGGGG:GGGGGGGG

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.

0.02157 (GGGGGGGG)

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

Links

OMIM: 133440.0001 dbSNP: rs142990298 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.
EIF4E		-	-	GRCh38 GRCh37	18	36

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.
Autism, susceptibility to, 19	risk factor (1)	no assertion criteria provided	Nov 1, 2009	RCV000033167.3

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.
risk factor (Nov 01, 2009)	no assertion criteria provided Method: literature only	AUTISM, SUSCEPTIBILITY TO, 19 Affected status: not provided Allele origin: germline	OMIM Accession: SCV000056949.3 First in ClinVar: Apr 04, 2013 Last updated: Oct 07, 2023	Publications: PubMed (1) PubMed: 19556253 Comment on evidence: In 2 probands with autism (AUTS19; 615091) from unrelated families, Neves-Pereira et al. (2009) detected the same single-basepair insertion of a C nucleotide at position … (more) In 2 probands with autism (AUTS19; 615091) from unrelated families, Neves-Pereira et al. (2009) detected the same single-basepair insertion of a C nucleotide at position -25 in the promoter region of the EIF4E gene. Each proband had an autistic sib, in whom the mutation was found; the mutation was also found in the fathers of all 4 affected children, but was not present in 2,040 control chromosomes. The insertion extended a run of 7 C nucleotides to 8 within the EIF4E basal promoter element (4EBE) that binds HNRNPK (600712). Neves-Pereira et al. (2009) performed electrophoretic mobility shift assays and reporter gene studies and showed that this mutation enhances binding of a nuclear factor, probably HNRNPK, and EIF4E promoter activity. Neves-Pereira et al. (2009) suggested that pharmacologic manipulation of EIF4E may provide therapeutic benefit for those with autism caused by disturbance of the converging pathways controlling EIF4E activity. (less)

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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Deregulation of EIF4E: a novel mechanism for autism.	Neves-Pereira M	Journal of medical genetics	2009	PMID: 19556253

Text-mined citations for rs142990298 ...

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 Dec 25, 2023

ClinVar Genomic variation as it relates to human health

NC_000004.12:g.98929153dup

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs142990298 ...