rs309370

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM5BP4_StrongBP6_Very_StrongBA1

The NM_152618.3(BBS12):c.1157G>A(p.Arg386Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,613,888 control chromosomes in the GnomAD database, including 116,672 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R386W) has been classified as Likely pathogenic.

Frequency

Genomes: 𝑓 0.42 ( 14660 hom., cov: 33)

Exomes 𝑓: 0.36 ( 102012 hom. )

Consequence

BBS12
NM_152618.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0820

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 -18 ACMG points.

PM5

Other missense variant is known to change same aminoacid residue: Variant chr4-122743048-C-T is described in Lovd as [Likely_pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=7.769768E-6).

BP6

Variant 4-122743049-G-A is Benign according to our data. Variant chr4-122743049-G-A is described in ClinVar as [Benign]. Clinvar id is 166725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-122743049-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS12	NM_152618.3 link	c.1157G>A	p.Arg386Gln	missense_variant	Exon 2 of 2	ENST00000314218.8	NP_689831.2	Q6ZW61
BBS12	NM_001178007.2 link	c.1157G>A	p.Arg386Gln	missense_variant	Exon 3 of 3		NP_001171478.1	Q6ZW61
BBS12	XM_011531680.3 link	c.1157G>A	p.Arg386Gln	missense_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.1157G>A	p.Arg386Gln	missense_variant	Exon 2 of 2	1	NM_152618.3	ENSP00000319062.3		Q6ZW61
BBS12	ENST00000542236.5 link	c.1157G>A	p.Arg386Gln	missense_variant	Exon 3 of 3	2		ENSP00000438273.1		Q6ZW61

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

64410

AN:

152020

Hom.:

14629

Cov.:

show subpopulations

Gnomad AFR

AF:

0.560

Gnomad AMI

AF:

0.370

Gnomad AMR

AF:

0.461

Gnomad ASJ

AF:

0.358

Gnomad EAS

AF:

0.646

Gnomad SAS

AF:

0.467

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.339

Gnomad OTH

AF:

0.420

GnomAD3 exomes

AF:

0.412

AC:

103503

AN:

251214

Hom.:

22936

AF XY:

0.408

AC XY:

55366

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.563

Gnomad AMR exome

AF:

0.489

Gnomad ASJ exome

AF:

0.365

Gnomad EAS exome

AF:

0.663

Gnomad SAS exome

AF:

0.473

Gnomad FIN exome

AF:

0.285

Gnomad NFE exome

AF:

0.340

Gnomad OTH exome

AF:

0.387

GnomAD4 exome

AF:

0.365

AC:

533043

AN:

1461750

Hom.:

102012

Cov.:

AF XY:

0.367

AC XY:

267119

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.561

Gnomad4 AMR exome

AF:

0.487

Gnomad4 ASJ exome

AF:

0.363

Gnomad4 EAS exome

AF:

0.672

Gnomad4 SAS exome

AF:

0.468

Gnomad4 FIN exome

AF:

0.292

Gnomad4 NFE exome

AF:

0.337

Gnomad4 OTH exome

AF:

0.393

GnomAD4 genome

AF:

0.424

AC:

64501

AN:

152138

Hom.:

14660

Cov.:

AF XY:

0.425

AC XY:

31587

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.561

Gnomad4 AMR

AF:

0.461

Gnomad4 ASJ

AF:

0.358

Gnomad4 EAS

AF:

0.647

Gnomad4 SAS

AF:

0.467

Gnomad4 FIN

AF:

0.276

Gnomad4 NFE

AF:

0.339

Gnomad4 OTH

AF:

0.421

Alfa

AF:

0.368

Hom.:

23089

Bravo

AF:

0.446

TwinsUK

AF:

0.333

AC:

1234

ALSPAC

AF:

0.329

AC:

1269

ESP6500AA

AF:

0.563

AC:

2479

ESP6500EA

AF:

0.338

AC:

2903

ExAC

AF:

0.414

AC:

50226

Asia WGS

AF:

0.594

AC:

2063

AN:

3478

EpiCase

AF:

0.341

EpiControl

AF:

0.339

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jan 21, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

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

Jun 15, 2021

Pars Genome Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 12, 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. -

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.1

DANN

Benign

0.76

DEOGEN2

Benign

0.078

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.23

T;.

MetaRNN

Benign

0.0000078

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.34

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

0.13

N;N

REVEL

Benign

0.065

Sift

Benign

0.57

T;T

Sift4G

Benign

0.52

T;T

Polyphen

0.0030

B;B

Vest4

0.019

MPC

0.097

ClinPred

0.0012

GERP RS

0.34

Varity_R

0.030

gMVP

0.28

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