4-122743272-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_152618.3(BBS12):c.1380G>C(p.Val460Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,614,036 control chromosomes in the GnomAD database, including 38,147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2503 hom., cov: 33)

Exomes 𝑓: 0.21 ( 35644 hom. )

Consequence

BBS12
NM_152618.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 2.20

Variant links:

Genes affected

BBS12 (HGNC:26648): (Bardet-Biedl syndrome 12) The protein encoded by this gene is part of a complex that is involved in membrane trafficking. The encoded protein is a molecular chaperone that aids in protein folding upon ATP hydrolysis. This protein also plays a role in adipocyte differentiation. Defects in this gene are a cause of Bardet-Biedl syndrome type 12. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, May 2010]

BBS12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 4-122743272-G-C is Benign according to our data. Variant chr4-122743272-G-C is described in ClinVar as [Benign]. Clinvar id is 166726.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-122743272-G-C is described in Lovd as [Likely_benign]. Variant chr4-122743272-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.2 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS12	NM_152618.3 link	c.1380G>C	p.Val460Val	synonymous_variant	Exon 2 of 2	ENST00000314218.8	NP_689831.2	Q6ZW61
BBS12	NM_001178007.2 link	c.1380G>C	p.Val460Val	synonymous_variant	Exon 3 of 3		NP_001171478.1	Q6ZW61
BBS12	XM_011531680.3 link	c.1380G>C	p.Val460Val	synonymous_variant	Exon 2 of 2		XP_011529982.1	Q6ZW61

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS12	ENST00000314218.8 link	c.1380G>C	p.Val460Val	synonymous_variant	Exon 2 of 2	1	NM_152618.3	ENSP00000319062.3		Q6ZW61
BBS12	ENST00000542236.5 link	c.1380G>C	p.Val460Val	synonymous_variant	Exon 3 of 3	2		ENSP00000438273.1		Q6ZW61

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24179

AN:

152104

Hom.:

2502

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0602

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.174

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.154

GnomAD3 exomes

AF:

0.168

AC:

42185

AN:

251398

Hom.:

4395

AF XY:

0.174

AC XY:

23618

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.0575

Gnomad AMR exome

AF:

0.0841

Gnomad ASJ exome

AF:

0.171

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.143

Gnomad FIN exome

AF:

0.200

Gnomad NFE exome

AF:

0.235

Gnomad OTH exome

AF:

0.185

GnomAD4 exome

AF:

0.212

AC:

310389

AN:

1461814

Hom.:

35644

Cov.:

AF XY:

0.212

AC XY:

154046

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0572

Gnomad4 AMR exome

AF:

0.0887

Gnomad4 ASJ exome

AF:

0.172

Gnomad4 EAS exome

AF:

0.000453

Gnomad4 SAS exome

AF:

0.144

Gnomad4 FIN exome

AF:

0.205

Gnomad4 NFE exome

AF:

0.238

Gnomad4 OTH exome

AF:

0.187

GnomAD4 genome

AF:

0.159

AC:

24178

AN:

152222

Hom.:

2503

Cov.:

AF XY:

0.154

AC XY:

11483

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0600

Gnomad4 AMR

AF:

0.126

Gnomad4 ASJ

AF:

0.174

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.133

Gnomad4 FIN

AF:

0.195

Gnomad4 NFE

AF:

0.234

Gnomad4 OTH

AF:

0.152

Alfa

AF:

0.169

Hom.:

863

Bravo

AF:

0.148

Asia WGS

AF:

0.0670

AC:

232

AN:

3478

EpiCase

AF:

0.227

EpiControl

AF:

0.225

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 21, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Bardet-Biedl syndrome 12

Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 15, 2021

Pars Genome Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Bardet-Biedl syndrome 1

Benign:2

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Bardet-Biedl syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

3.1

DANN

Benign

0.75

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