rs17006092

Positions:

Variant summary

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

The NM_152618.3(BBS12):c.1209G>A(p.Val403=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 1,614,194 control chromosomes in the GnomAD database, including 551 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 170 hom., cov: 33)

Exomes 𝑓: 0.018 ( 381 hom. )

Consequence

BBS12
NM_152618.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.831

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=-0.87).

BP6

Variant 4-122743101-G-A is Benign according to our data. Variant chr4-122743101-G-A is described in ClinVar as [Benign]. Clinvar id is 262670.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-122743101-G-A is described in Lovd as [Benign]. Variant chr4-122743101-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.831 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0769 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.1209G>A	p.Val403=	synonymous_variant	2/2	ENST00000314218.8	NP_689831.2
BBS12	NM_001178007.2 linkuse as main transcript	c.1209G>A	p.Val403=	synonymous_variant	3/3		NP_001171478.1
BBS12	XM_011531680.3 linkuse as main transcript	c.1209G>A	p.Val403=	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.1209G>A	p.Val403=	synonymous_variant	2/2	1	NM_152618.3	ENSP00000319062	P1
BBS12	ENST00000542236.5 linkuse as main transcript	c.1209G>A	p.Val403=	synonymous_variant	3/3	2		ENSP00000438273	P1

Frequencies

GnomAD3 genomes

AF:

0.0331

AC:

5043

AN:

152214

Hom.:

167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0787

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0245

Gnomad ASJ

AF:

0.0277

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00320

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0175

Gnomad OTH

AF:

0.0378

GnomAD3 exomes

AF:

0.0174

AC:

4380

AN:

251454

Hom.:

AF XY:

0.0159

AC XY:

2159

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.0815

Gnomad AMR exome

AF:

0.0146

Gnomad ASJ exome

AF:

0.0290

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00134

Gnomad FIN exome

AF:

0.00443

Gnomad NFE exome

AF:

0.0175

Gnomad OTH exome

AF:

0.0215

GnomAD4 exome

AF:

0.0182

AC:

26630

AN:

1461862

Hom.:

381

Cov.:

AF XY:

0.0173

AC XY:

12608

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0771

Gnomad4 AMR exome

AF:

0.0158

Gnomad4 ASJ exome

AF:

0.0298

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00115

Gnomad4 FIN exome

AF:

0.00565

Gnomad4 NFE exome

AF:

0.0186

Gnomad4 OTH exome

AF:

0.0226

GnomAD4 genome

AF:

0.0333

AC:

5067

AN:

152332

Hom.:

170

Cov.:

AF XY:

0.0322

AC XY:

2398

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0791

Gnomad4 AMR

AF:

0.0243

Gnomad4 ASJ

AF:

0.0277

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00320

Gnomad4 NFE

AF:

0.0175

Gnomad4 OTH

AF:

0.0374

Alfa

AF:

0.0209

Hom.:

Bravo

AF:

0.0370

Asia WGS

AF:

0.00982

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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	-	- -

Bardet-Biedl syndrome 1

Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	Apr 19, 2017	- -
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:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Bardet-Biedl syndrome 12

Benign:2

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
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. -

Bardet-Biedl syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.077

DANN

Benign

0.52

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