rs77731085

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000314218.8(BBS12):c.355G>A(p.Gly119Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000938 in 1,613,782 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G119D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0041 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00061 ( 4 hom. )

Consequence

BBS12
ENST00000314218.8 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 7.11

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009709686).

BP6

Variant 4-122742247-G-A is Benign according to our data. Variant chr4-122742247-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 215543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-122742247-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00411 (626/152244) while in subpopulation AFR AF= 0.0135 (561/41522). AF 95% confidence interval is 0.0126. There are 3 homozygotes in gnomad4. There are 313 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
BBS12	NM_152618.3 linkuse as main transcript	c.355G>A	p.Gly119Ser	missense_variant	2/2	ENST00000314218.8	NP_689831.2
BBS12	NM_001178007.2 linkuse as main transcript	c.355G>A	p.Gly119Ser	missense_variant	3/3		NP_001171478.1
BBS12	XM_011531680.3 linkuse as main transcript	c.355G>A	p.Gly119Ser	missense_variant	2/2		XP_011529982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
BBS12	ENST00000314218.8 linkuse as main transcript	c.355G>A	p.Gly119Ser	missense_variant	2/2	1	NM_152618.3	ENSP00000319062	P1
BBS12	ENST00000542236.5 linkuse as main transcript	c.355G>A	p.Gly119Ser	missense_variant	3/3	2		ENSP00000438273	P1
BBS12	ENST00000433287.1 linkuse as main transcript	c.355G>A	p.Gly119Ser	missense_variant	3/3	2		ENSP00000398912

Frequencies

GnomAD3 genomes

AF:

0.00411

AC:

625

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00160

AC:

398

AN:

249482

Hom.:

AF XY:

0.00115

AC XY:

155

AN XY:

135044

show subpopulations

Gnomad AFR exome

AF:

0.0142

Gnomad AMR exome

AF:

0.00185

Gnomad ASJ exome

AF:

0.00589

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000321

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.000608

AC:

888

AN:

1461538

Hom.:

Cov.:

AF XY:

0.000494

AC XY:

359

AN XY:

727056

show subpopulations

Gnomad4 AFR exome

AF:

0.0128

Gnomad4 AMR exome

AF:

0.00212

Gnomad4 ASJ exome

AF:

0.00505

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000121

Gnomad4 OTH exome

AF:

0.00137

GnomAD4 genome

AF:

0.00411

AC:

626

AN:

152244

Hom.:

Cov.:

AF XY:

0.00420

AC XY:

313

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0135

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.000974

Hom.:

Bravo

AF:

0.00485

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0116

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00175

AC:

213

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000356

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	May 03, 2022	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Nov 17, 2020	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	BBS12: BS1, BS2 -

Bardet-Biedl syndrome 12

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Sep 28, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

Bardet-Biedl syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	research	Biomedical Genomics and Oncogenetics Laboratory, Institut Pasteur de Tunis, University Tunis El Manar	Nov 01, 2022	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

D;D;.

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.73

T;.;T

MetaRNN

Benign

0.0097

T;T;T

MetaSVM

Uncertain

0.028

MutationAssessor

Uncertain

2.8

M;M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.4

N;N;N

REVEL

Uncertain

0.58

Sift

Benign

0.072

T;T;D

Sift4G

Benign

0.12

T;T;D

Polyphen

1.0

D;D;.

Vest4

0.78

MVP

0.88

MPC

0.45

ClinPred

0.019

GERP RS

5.2

Varity_R

0.39

gMVP

0.59

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