NM_033028.5(BBS4):c.1462A>G (p.Thr488Ala) AND Bardet-Biedl syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 13, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001359360.6

Allele description [Variation Report for NM_033028.5(BBS4):c.1462A>G (p.Thr488Ala)]

NM_033028.5(BBS4):c.1462A>G (p.Thr488Ala)

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.1462A>G (p.Thr488Ala)

HGVS:

NC_000015.10:g.72737489A>G
NG_009416.2:g.56305A>G
NM_001252678.2:c.946A>G
NM_001320665.2:c.1393A>G
NM_033028.5:c.1462A>GMANE SELECT
NP_001239607.1:p.Thr316Ala
NP_001307594.1:p.Thr465Ala
NP_149017.2:p.Thr488Ala
NC_000015.9:g.73029830A>G
NR_045565.2:n.1541A>G
NR_045566.2:n.1796A>G

Protein change:

T316A

Links:

dbSNP: rs746070171

NCBI 1000 Genomes Browser:

rs746070171

Molecular consequence:

NM_001252678.2:c.946A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001320665.2:c.1393A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_033028.5:c.1462A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_045565.2:n.1541A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_045566.2:n.1796A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Bardet-Biedl syndrome (BBS)
Identifiers:: MONDO: MONDO:0015229; MedGen: C0752166; Orphanet: 110; OMIM: PS209900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001555224	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 13, 2022)	germline	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

SCV001555224

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 13, 2022)

germline

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001555224.3

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

Description

This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 488 of the BBS4 protein (p.Thr488Ala). This variant is present in population databases (rs746070171, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with BBS4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1051338). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine