rs28507107

Positions:

chr4-122743739-G-A

Variant summary

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

The ENST00000314218.8(BBS12):c.1847G>A(p.Ser616Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00481 in 1,614,134 control chromosomes in the GnomAD database, including 317 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 174 hom., cov: 33)

Exomes 𝑓: 0.0026 ( 143 hom. )

Consequence

BBS12
ENST00000314218.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: 2.64

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=0.0016806126).

BP6

Variant 4-122743739-G-A is Benign according to our data. Variant chr4-122743739-G-A is described in ClinVar as [Benign]. Clinvar id is 100565.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-122743739-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.087 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.1847G>A	p.Ser616Asn	missense_variant	2/2	ENST00000314218.8	NP_689831.2
BBS12	NM_001178007.2 linkuse as main transcript	c.1847G>A	p.Ser616Asn	missense_variant	3/3		NP_001171478.1
BBS12	XM_011531680.3 linkuse as main transcript	c.1847G>A	p.Ser616Asn	missense_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.1847G>A	p.Ser616Asn	missense_variant	2/2	1	NM_152618.3	ENSP00000319062	P1
BBS12	ENST00000542236.5 linkuse as main transcript	c.1847G>A	p.Ser616Asn	missense_variant	3/3	2		ENSP00000438273	P1

Frequencies

GnomAD3 genomes

AF:

0.0259

AC:

3937

AN:

152182

Hom.:

174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00903

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.0239

GnomAD3 exomes

AF:

0.00668

AC:

1679

AN:

251260

Hom.:

AF XY:

0.00494

AC XY:

671

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.0914

Gnomad AMR exome

AF:

0.00399

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000308

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00261

AC:

3816

AN:

1461834

Hom.:

143

Cov.:

AF XY:

0.00229

AC XY:

1664

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0892

Gnomad4 AMR exome

AF:

0.00481

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000222

Gnomad4 OTH exome

AF:

0.00545

GnomAD4 genome

AF:

0.0259

AC:

3947

AN:

152300

Hom.:

174

Cov.:

AF XY:

0.0253

AC XY:

1885

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0894

Gnomad4 AMR

AF:

0.00901

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.0237

Alfa

AF:

0.00480

Hom.:

Bravo

AF:

0.0292

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0912

AC:

402

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.00860

AC:

1044

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Bardet-Biedl syndrome 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -

Bardet-Biedl syndrome 12

Benign:2

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	- -

not provided

Benign:1Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	literature only	NEI Ophthalmic Genomics Laboratory, National Institutes of Health	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.48

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.53

T;.

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.33

N;N

REVEL

Benign

0.13

Sift

Benign

0.38

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.0030

B;B

Vest4

0.062

MVP

0.62

MPC

0.089

ClinPred

0.0061

GERP RS

1.1

Varity_R

0.042

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