rs2292493

Positions:

chr4-122743290-C-T

Variant summary

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

The NM_152618.3(BBS12):c.1398C>T(p.Gly466=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,613,970 control chromosomes in the GnomAD database, including 26,699 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2915 hom., cov: 33)

Exomes 𝑓: 0.13 ( 23784 hom. )

Consequence

BBS12
NM_152618.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.621

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=-0.69).

BP6

Variant 4-122743290-C-T is Benign according to our data. Variant chr4-122743290-C-T is described in ClinVar as [Benign]. Clinvar id is 262672.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-122743290-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.621 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
BBS12	NM_152618.3 linkuse as main transcript	c.1398C>T	p.Gly466=	synonymous_variant	2/2	ENST00000314218.8	NP_689831.2
BBS12	NM_001178007.2 linkuse as main transcript	c.1398C>T	p.Gly466=	synonymous_variant	3/3		NP_001171478.1
BBS12	XM_011531680.3 linkuse as main transcript	c.1398C>T	p.Gly466=	synonymous_variant	2/2		XP_011529982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS12	ENST00000314218.8 linkuse as main transcript	c.1398C>T	p.Gly466=	synonymous_variant	2/2	1	NM_152618.3	ENSP00000319062	P1
BBS12	ENST00000542236.5 linkuse as main transcript	c.1398C>T	p.Gly466=	synonymous_variant	3/3	2		ENSP00000438273	P1

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23139

AN:

151998

Hom.:

2907

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.203

Gnomad AMR

AF:

0.283

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.644

Gnomad SAS

AF:

0.347

Gnomad FIN

AF:

0.0771

Gnomad MID

AF:

0.255

Gnomad NFE

AF:

0.0898

Gnomad OTH

AF:

0.164

GnomAD3 exomes

AF:

0.209

AC:

52549

AN:

251410

Hom.:

9522

AF XY:

0.207

AC XY:

28107

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.379

Gnomad ASJ exome

AF:

0.150

Gnomad EAS exome

AF:

0.662

Gnomad SAS exome

AF:

0.344

Gnomad FIN exome

AF:

0.0803

Gnomad NFE exome

AF:

0.0892

Gnomad OTH exome

AF:

0.172

GnomAD4 exome

AF:

0.129

AC:

188509

AN:

1461854

Hom.:

23784

Cov.:

AF XY:

0.135

AC XY:

97894

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.141

Gnomad4 AMR exome

AF:

0.370

Gnomad4 ASJ exome

AF:

0.147

Gnomad4 EAS exome

AF:

0.671

Gnomad4 SAS exome

AF:

0.338

Gnomad4 FIN exome

AF:

0.0811

Gnomad4 NFE exome

AF:

0.0826

Gnomad4 OTH exome

AF:

0.168

GnomAD4 genome

AF:

0.152

AC:

23172

AN:

152116

Hom.:

2915

Cov.:

AF XY:

0.161

AC XY:

11958

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.139

Gnomad4 AMR

AF:

0.283

Gnomad4 ASJ

AF:

0.149

Gnomad4 EAS

AF:

0.645

Gnomad4 SAS

AF:

0.346

Gnomad4 FIN

AF:

0.0771

Gnomad4 NFE

AF:

0.0898

Gnomad4 OTH

AF:

0.168

Alfa

AF:

0.124

Hom.:

1734

Bravo

AF:

0.170

Asia WGS

AF:

0.509

AC:

1766

AN:

3478

EpiCase

AF:

0.0997

EpiControl

AF:

0.0984

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Bardet-Biedl syndrome 12

Benign:3

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. -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 15, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

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

-0.69

CADD

Benign

7.1

DANN

Benign

0.38

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