rs309371

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.1200G>A(p.Val400Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0311 in 1,614,144 control chromosomes in the GnomAD database, including 3,323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.090 ( 1610 hom., cov: 33)

Exomes 𝑓: 0.025 ( 1713 hom. )

Consequence

BBS12
NM_152618.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.08

Publications

9 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=-0.91).

BP6

Variant 4-122743092-G-A is Benign according to our data. Variant chr4-122743092-G-A is described in ClinVar as Benign. ClinVar VariationId is 262669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.08 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
BBS12	NM_152618.3 link	c.1200G>A	p.Val400Val	synonymous_variant	Exon 2 of 2	ENST00000314218.8	NP_689831.2
BBS12	NM_001178007.2 link	c.1200G>A	p.Val400Val	synonymous_variant	Exon 3 of 3		NP_001171478.1
BBS12	XM_011531680.3 link	c.1200G>A	p.Val400Val	synonymous_variant	Exon 2 of 2		XP_011529982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS12	ENST00000314218.8 link	c.1200G>A	p.Val400Val	synonymous_variant	Exon 2 of 2	1	NM_152618.3	ENSP00000319062.3
BBS12	ENST00000542236.5 link	c.1200G>A	p.Val400Val	synonymous_variant	Exon 3 of 3	2		ENSP00000438273.1

Frequencies

GnomAD3 genomes

AF:

0.0903

AC:

13740

AN:

152190

Hom.:

1598

Cov.:

show subpopulations

Gnomad AFR

AF:

0.275

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0450

Gnomad ASJ

AF:

0.0435

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00320

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0187

Gnomad OTH

AF:

0.0827

GnomAD2 exomes

AF:

0.0335

AC:

8420

AN:

251430

AF XY:

0.0279

show subpopulations

Gnomad AFR exome

AF:

0.279

Gnomad AMR exome

AF:

0.0258

Gnomad ASJ exome

AF:

0.0489

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00443

Gnomad NFE exome

AF:

0.0189

Gnomad OTH exome

AF:

0.0329

GnomAD4 exome

AF:

0.0249

AC:

36363

AN:

1461836

Hom.:

1713

Cov.:

AF XY:

0.0232

AC XY:

16840

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.281

AC:

9391

AN:

33478

American (AMR)

AF:

0.0287

AC:

1283

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0494

AC:

1291

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00181

AC:

156

AN:

86258

European-Finnish (FIN)

AF:

0.00565

AC:

302

AN:

53420

Middle Eastern (MID)

AF:

0.0296

AC:

171

AN:

5768

European-Non Finnish (NFE)

AF:

0.0193

AC:

21485

AN:

1111960

Other (OTH)

AF:

0.0378

AC:

2283

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

2070

4140

6210

8280

10350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

972

1944

2916

3888

4860

<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:

0.0905

AC:

13780

AN:

152308

Hom.:

1610

Cov.:

AF XY:

0.0874

AC XY:

6510

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.276

AC:

11445

AN:

41530

American (AMR)

AF:

0.0448

AC:

686

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0435

AC:

151

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00103

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00320

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0187

AC:

1273

AN:

68036

Other (OTH)

AF:

0.0818

AC:

173

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

561

1122

1683

2244

2805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<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:

0.0453

Hom.:

885

Bravo

AF:

0.104

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

not provided

Benign:2

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Bardet-Biedl syndrome 12

Benign:2

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

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

-0.91

CADD

Benign

0.015

(source)

DANN

Benign

0.50

PhyloP100

-1.1

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