chr9-33255903-T-C

Position:

chr9-33255903-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004323.6(BAG1):c.910A>G(p.Ser304Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00197 in 1,614,052 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 27 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 33 hom. )

Consequence

BAG1
NM_004323.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.97

Variant links:

Genes affected

BAG1 (HGNC:937): (BAG cochaperone 1) The oncogene BCL2 is a membrane protein that blocks a step in a pathway leading to apoptosis or programmed cell death. The protein encoded by this gene binds to BCL2 and is referred to as BCL2-associated athanogene. It enhances the anti-apoptotic effects of BCL2 and represents a link between growth factor receptors and anti-apoptotic mechanisms. Multiple protein isoforms are encoded by this mRNA through the use of a non-AUG (CUG) initiation codon, and three alternative downstream AUG initiation codons. A related pseudogene has been defined on chromosome X. [provided by RefSeq, Feb 2010]

BAG1 links:

BAG1 (HGNC:):

BAG1 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=0.011676848).

BP6

Variant 9-33255903-T-C is Benign according to our data. Variant chr9-33255903-T-C is described in ClinVar as [Benign]. Clinvar id is 785282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0107 (1631/152336) while in subpopulation AFR AF= 0.0378 (1571/41570). AF 95% confidence interval is 0.0362. There are 27 homozygotes in gnomad4. There are 769 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BAG1	NM_004323.6 linkuse as main transcript	c.910A>G	p.Ser304Gly	missense_variant	6/7	ENST00000634734.3	NP_004314.6	Q99933-1
BAG1	NM_001349286.2 linkuse as main transcript	c.697A>G	p.Ser233Gly	missense_variant	6/7		NP_001336215.1
BAG1	NM_001172415.2 linkuse as main transcript	c.565A>G	p.Ser189Gly	missense_variant	6/7		NP_001165886.1	Q99933-4
BAG1	NM_001349299.2 linkuse as main transcript	c.496A>G	p.Ser166Gly	missense_variant	6/7		NP_001336228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAG1	ENST00000634734.3 linkuse as main transcript	c.910A>G	p.Ser304Gly	missense_variant	6/7	1	NM_004323.6	ENSP00000489189.2		Q99933-1J3QTA2

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1629

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0378

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00276

AC:

693

AN:

251402

Hom.:

AF XY:

0.00207

AC XY:

281

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.0386

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000792

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00106

AC:

1544

AN:

1461716

Hom.:

Cov.:

AF XY:

0.000916

AC XY:

666

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.0383

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000261

Gnomad4 OTH exome

AF:

0.00238

GnomAD4 genome

AF:

0.0107

AC:

1631

AN:

152336

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

769

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0378

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00184

Hom.:

Bravo

AF:

0.0124

ESP6500AA

AF:

0.0391

AC:

172

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00325

AC:

394

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.65

.;.;D

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.88

D;D;D

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Uncertain

-0.22

MutationAssessor

Benign

1.1

.;.;L

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.7

.;N;.

REVEL

Uncertain

0.50

Sift

Benign

0.38

.;T;.

Sift4G

Benign

0.29

T;T;.

Polyphen

1.0

.;.;D

Vest4

0.59

MVP

0.88

ClinPred

0.039

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.48

gMVP

0.33

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