NM_033028.5(BBS4):c.712-1G>A AND Bardet-Biedl syndrome 4

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Feb 15, 2024
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000778446.11

Allele description [Variation Report for NM_033028.5(BBS4):c.712-1G>A]

NM_033028.5(BBS4):c.712-1G>A

Gene:

BBS4:Bardet-Biedl syndrome 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q24.1

Genomic location:

Preferred name:

NM_033028.5(BBS4):c.712-1G>A

HGVS:

NC_000015.10:g.72731304G>A
NG_009416.2:g.50120G>A
NG_009416.3:g.50099G>A
NM_001252678.2:c.196-1G>A
NM_001320665.2:c.643-1G>A
NM_033028.5:c.712-1G>AMANE SELECT
NC_000015.9:g.73023645G>A
NM_033028.3:c.712-1G>A
NM_033028.4:c.712-1G>A

Links:

dbSNP: rs377031435

NCBI 1000 Genomes Browser:

rs377031435

Molecular consequence:

NM_001252678.2:c.196-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001320665.2:c.643-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_033028.5:c.712-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Bardet-Biedl syndrome 4 (BBS4)
Identifiers:: MONDO: MONDO:0014433; MedGen: C2936864; Orphanet: 110; OMIM: 615982

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000914694	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Uncertain significance (Sep 7, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV001760351	Genomics England Pilot Project, Genomics England	no assertion criteria provided (ACGS Guidelines, 2016)	Likely pathogenic	germline	clinical testing	Citation Link,
SCV004214089	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 15, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000914694

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)

Uncertain significance
(Sep 7, 2017)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link,

SCV001760351

Genomics England Pilot Project, Genomics England

no assertion criteria provided

(ACGS Guidelines, 2016)

Likely pathogenic

germline

clinical testing

Citation Link,

SCV004214089

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 15, 2024)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular findings from 537 individuals with inherited retinal disease.

Ellingford JM, Barton S, Bhaskar S, O'Sullivan J, Williams SG, Lamb JA, Panda B, Sergouniotis PI, Gillespie RL, Daiger SP, Hall G, Gale T, Lloyd IC, Bishop PN, Ramsden SC, Black GCM.

J Med Genet. 2016 Nov;53(11):761-767. doi: 10.1136/jmedgenet-2016-103837. Epub 2016 May 11.

PubMed [citation]

PMID:: 27208204
PMCID:: PMC5106339

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000914694.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The BBS4 c.712-1G>A variant occurs in a canonical splice site (acceptor) and is therefore predicted to disrupt or distort the normal gene product. The c.712-1G>A variant has been identified in one study in which it was found in a homozygous state in one individual with Bardet-Biedl syndrome (Ellingford et al. 2016). Control data are unavailable for this variant, which is reported at a frequency of 0.000040 in the European (non-Finnish) population of the Genome Aggregation Database. Based on the limited evidence and the potential impact of splice acceptor variants, the c.712-1G>A variant is classified as a variant of unknown significance but suspicious for pathogenicity for Bardet-Biedl syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genomics England Pilot Project, Genomics England, SCV001760351.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004214089.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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