rs13135445

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_152618.3(BBS12):c.1410C>T(p.Cys470Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,613,942 control chromosomes in the GnomAD database, including 43,428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3071 hom., cov: 33)

Exomes 𝑓: 0.23 ( 40357 hom. )

Consequence

BBS12
NM_152618.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0170

Publications

15 publications found

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 Gene-Disease associations (from GenCC):

Bardet-Biedl syndrome 12
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P, Ambry Genetics, Myriad Women’s Health
ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Bardet-Biedl syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

BBS12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 4-122743302-C-T is Benign according to our data. Variant chr4-122743302-C-T is described in ClinVar as Benign. ClinVar VariationId is 166728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.017 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS12	NM_152618.3 link	c.1410C>T	p.Cys470Cys	synonymous_variant	Exon 2 of 2	ENST00000314218.8	NP_689831.2	Q6ZW61
BBS12	NM_001178007.2 link	c.1410C>T	p.Cys470Cys	synonymous_variant	Exon 3 of 3		NP_001171478.1	Q6ZW61
BBS12	XM_011531680.3 link	c.1410C>T	p.Cys470Cys	synonymous_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.1410C>T	p.Cys470Cys	synonymous_variant	Exon 2 of 2	1	NM_152618.3	ENSP00000319062.3		Q6ZW61
BBS12	ENST00000542236.5 link	c.1410C>T	p.Cys470Cys	synonymous_variant	Exon 3 of 3	2		ENSP00000438273.1		Q6ZW61

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28381

AN:

152074

Hom.:

3071

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.147

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.199

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.187

GnomAD2 exomes

AF:

0.181

AC:

45613

AN:

251400

AF XY:

0.186

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.0964

Gnomad ASJ exome

AF:

0.195

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.204

Gnomad NFE exome

AF:

0.249

Gnomad OTH exome

AF:

0.202

GnomAD4 exome

AF:

0.227

AC:

331753

AN:

1461750

Hom.:

40357

Cov.:

AF XY:

0.225

AC XY:

163917

AN XY:

727178

show subpopulations

African (AFR)

AF:

0.123

AC:

4121

AN:

33480

American (AMR)

AF:

0.102

AC:

4554

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

5116

AN:

26136

East Asian (EAS)

AF:

0.000479

AC:

AN:

39700

South Asian (SAS)

AF:

0.138

AC:

11915

AN:

86256

European-Finnish (FIN)

AF:

0.211

AC:

11247

AN:

53408

Middle Eastern (MID)

AF:

0.174

AC:

1003

AN:

5768

European-Non Finnish (NFE)

AF:

0.253

AC:

281405

AN:

1111884

Other (OTH)

AF:

0.205

AC:

12373

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

14632

29264

43897

58529

73161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9272

18544

27816

37088

46360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.187

AC:

28386

AN:

152192

Hom.:

3071

Cov.:

AF XY:

0.181

AC XY:

13459

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.128

AC:

5315

AN:

41528

American (AMR)

AF:

0.146

AC:

2240

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

671

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5190

South Asian (SAS)

AF:

0.127

AC:

611

AN:

4824

European-Finnish (FIN)

AF:

0.199

AC:

2099

AN:

10574

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.248

AC:

16851

AN:

67988

Other (OTH)

AF:

0.184

AC:

390

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1176

2353

3529

4706

5882

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

308

616

924

1232

1540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.219

Hom.:

4066

Bravo

AF:

0.179

Asia WGS

AF:

0.0710

AC:

247

AN:

3478

EpiCase

AF:

0.240

EpiControl

AF:

0.238

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

- -

Jan 13, 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. -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Bardet-Biedl syndrome 1

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 04, 2021

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

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.72

(source)

DANN

Benign

0.23

PhyloP100

-0.017

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over