rs13135778

Variant summary

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

The NM_152618.3(BBS12):c.1399G>A(p.Asp467Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,613,942 control chromosomes in the GnomAD database, including 37,042 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 (★★). Synonymous variant affecting the same amino acid position (i.e. D467D) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.16 ( 2432 hom., cov: 33)

Exomes 𝑓: 0.21 ( 34610 hom. )

Consequence

BBS12
NM_152618.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.624

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=0.0021182895).

BP6

Variant 4-122743291-G-A is Benign according to our data. Variant chr4-122743291-G-A is described in ClinVar as [Benign]. Clinvar id is 166727.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-122743291-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BBS12	NM_152618.3 linkuse as main transcript	c.1399G>A	p.Asp467Asn	missense_variant	2/2	ENST00000314218.8
BBS12	NM_001178007.2 linkuse as main transcript	c.1399G>A	p.Asp467Asn	missense_variant	3/3
BBS12	XM_011531680.3 linkuse as main transcript	c.1399G>A	p.Asp467Asn	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS12	ENST00000314218.8 linkuse as main transcript	c.1399G>A	p.Asp467Asn	missense_variant	2/2	1	NM_152618.3	P1
BBS12	ENST00000542236.5 linkuse as main transcript	c.1399G>A	p.Asp467Asn	missense_variant	3/3	2		P1

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23917

AN:

152102

Hom.:

2432

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0626

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.166

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.230

Gnomad OTH

AF:

0.153

GnomAD3 exomes

AF:

0.165

AC:

41447

AN:

251378

Hom.:

4242

AF XY:

0.170

AC XY:

23139

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.0609

Gnomad AMR exome

AF:

0.0826

Gnomad ASJ exome

AF:

0.166

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.137

Gnomad FIN exome

AF:

0.200

Gnomad NFE exome

AF:

0.231

Gnomad OTH exome

AF:

0.181

GnomAD4 exome

AF:

0.209

AC:

305671

AN:

1461722

Hom.:

34610

Cov.:

AF XY:

0.208

AC XY:

151534

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.0603

Gnomad4 AMR exome

AF:

0.0868

Gnomad4 ASJ exome

AF:

0.166

Gnomad4 EAS exome

AF:

0.000453

Gnomad4 SAS exome

AF:

0.137

Gnomad4 FIN exome

AF:

0.205

Gnomad4 NFE exome

AF:

0.234

Gnomad4 OTH exome

AF:

0.183

GnomAD4 genome

AF:

0.157

AC:

23917

AN:

152220

Hom.:

2432

Cov.:

AF XY:

0.153

AC XY:

11362

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0625

Gnomad4 AMR

AF:

0.123

Gnomad4 ASJ

AF:

0.166

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.126

Gnomad4 FIN

AF:

0.195

Gnomad4 NFE

AF:

0.230

Gnomad4 OTH

AF:

0.150

Alfa

AF:

0.207

Hom.:

7416

Bravo

AF:

0.146

TwinsUK

AF:

0.231

AC:

856

ALSPAC

AF:

0.230

AC:

888

ESP6500AA

AF:

0.0690

AC:

304

ESP6500EA

AF:

0.226

AC:

1941

ExAC

AF:

0.170

AC:

20587

Asia WGS

AF:

0.0640

AC:

224

AN:

3478

EpiCase

AF:

0.222

EpiControl

AF:

0.220

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 21, 2014	- -
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+	-	- -

Bardet-Biedl syndrome 12

Benign:3

Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

Bardet-Biedl syndrome 1

Benign:2

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	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Bardet-Biedl syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

Cadd

Benign

2.8

Dann

Benign

0.24

DEOGEN2

Benign

0.087

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.13

T;.

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-2.1

N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

0.95

N;N

REVEL

Benign

0.15

Sift

Benign

1.0

T;T

Sift4G

Benign

0.96

T;T

Polyphen

0.0

B;B

Vest4

0.018

MPC

0.081

ClinPred

0.00029

GERP RS

1.9

Varity_R

0.031

gMVP

0.20

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