Variant rs2298806 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024649.5(BBS1):c.378G>A(p.Leu126Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,613,210 control chromosomes in the GnomAD database, including 45,934 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3877 hom., cov: 32)

Exomes 𝑓: 0.24 ( 42057 hom. )

Consequence

BBS1
NM_024649.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 1.14

Variant links:

Genes affected

BBS1 (HGNC:966): (Bardet-Biedl syndrome 1) Mutations in this gene have been observed in patients with the major form (type 1) of Bardet-Biedl syndrome. The encoded protein may play a role in eye, limb, cardiac and reproductive system development. [provided by RefSeq, Jul 2008]

BBS1 links:

ENSG00000256349 (HGNC:):

ENSG00000256349 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 11-66514624-G-A is Benign according to our data. Variant chr11-66514624-G-A is described in ClinVar as [Benign]. Clinvar id is 261750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-66514624-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS1	NM_024649.5 linkuse as main transcript	c.378G>A	p.Leu126Leu	synonymous_variant	4/17	ENST00000318312.12	NP_078925.3	Q8NFJ9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS1	ENST00000318312.12 linkuse as main transcript	c.378G>A	p.Leu126Leu	synonymous_variant	4/17	1	NM_024649.5	ENSP00000317469.7		Q8NFJ9-1
ENSG00000256349	ENST00000419755.3 linkuse as main transcript	c.489G>A	p.Leu163Leu	synonymous_variant	4/17	2		ENSP00000398526.3

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32259

AN:

151952

Hom.:

3870

Cov.:

show subpopulations

Gnomad AFR

AF:

0.135

Gnomad AMI

AF:

0.257

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.268

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.387

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.179

GnomAD3 exomes

AF:

0.224

AC:

56195

AN:

250730

Hom.:

6918

AF XY:

0.227

AC XY:

30842

AN XY:

135580

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.141

Gnomad ASJ exome

AF:

0.168

Gnomad EAS exome

AF:

0.269

Gnomad SAS exome

AF:

0.208

Gnomad FIN exome

AF:

0.379

Gnomad NFE exome

AF:

0.237

Gnomad OTH exome

AF:

0.210

GnomAD4 exome

AF:

0.235

AC:

344006

AN:

1461140

Hom.:

42057

Cov.:

AF XY:

0.236

AC XY:

171356

AN XY:

726920

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.144

Gnomad4 ASJ exome

AF:

0.168

Gnomad4 EAS exome

AF:

0.261

Gnomad4 SAS exome

AF:

0.215

Gnomad4 FIN exome

AF:

0.372

Gnomad4 NFE exome

AF:

0.240

Gnomad4 OTH exome

AF:

0.221

GnomAD4 genome

AF:

0.212

AC:

32278

AN:

152070

Hom.:

3877

Cov.:

AF XY:

0.217

AC XY:

16144

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.135

Gnomad4 AMR

AF:

0.170

Gnomad4 ASJ

AF:

0.151

Gnomad4 EAS

AF:

0.268

Gnomad4 SAS

AF:

0.202

Gnomad4 FIN

AF:

0.387

Gnomad4 NFE

AF:

0.242

Gnomad4 OTH

AF:

0.176

Alfa

AF:

0.226

Hom.:

5793

Bravo

AF:

0.191

Asia WGS

AF:

0.239

AC:

831

AN:

3478

EpiCase

AF:

0.222

EpiControl

AF:

0.228

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Bardet-Biedl syndrome 1

Benign:6

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 02, 2017	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Nov 15, 2016	Variant summary: The BBS1 c.378G>A (p.Leu126Leu) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Mutation taster predicts a polymorphism outcome for this variant along with 5/5 splice prediction tools predicting the variant not to have an impact on normal splicing. This variant was found in 27024/121032 control chromosomes (3285 homozygotes) at a frequency of 0.2232798, which greatly exceeds the estimated maximal expected allele frequency of a pathogenic BBS1 variant (0.0009449), suggesting this variant is likely a benign polymorphism. A clinical diagnostic laboratory and at least one publication classified this variant as benign. Taken together, this variant is classified as benign. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Retinal dystrophy

Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Bardet-Biedl syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over