rs368034599

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PVS1_SupportingPM2BP6_Moderate

The ENST00000379704.7(BAG1):c.1A>G(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,612,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

BAG1
ENST00000379704.7 start_lost

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.781

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PVS1

Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 24 codons. Genomic position: 33264260. Lost 0.101 part of the original CDS.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 9-33264329-T-C is Benign according to our data. Variant chr9-33264329-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3132797.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAG1	NM_004323.6 link	c.346A>G	p.Met116Val	missense_variant	Exon 1 of 7	ENST00000634734.3	NP_004314.6	Q99933-1
BAG1	NM_001172415.2 link	c.1A>G	p.Met1?	start_lost	Exon 1 of 7		NP_001165886.1	Q99933-4
BAG1	NM_001349286.2 link	c.133A>G	p.Met45Val	missense_variant	Exon 1 of 7		NP_001336215.1
BAG1	NM_001349299.2 link	c.-69A>G		5_prime_UTR_variant	Exon 1 of 7		NP_001336228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAG1	ENST00000634734.3 link	c.346A>G	p.Met116Val	missense_variant	Exon 1 of 7	1	NM_004323.6	ENSP00000489189.2		Q99933-1J3QTA2

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

151106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000443

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251370

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

1112000

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000199

AC:

AN:

151106

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73756

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40986

American (AMR)

AF:

0.00

AC:

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5134

South Asian (SAS)

AF:

0.00

AC:

AN:

4758

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10472

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000443

AC:

AN:

67776

Other (OTH)

AF:

0.00

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 22, 2023

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.51

CADD

Benign

2.4

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.12

.;.;T;T;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.38

T;D;T;D;D;.

M_CAP

Benign

0.0025

MetaRNN

Benign

0.033

T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.83

.;.;N;.;.;.

PhyloP100

-0.78

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.18

.;N;.;N;.;D

REVEL

Benign

0.043

Sift

Benign

0.60

.;T;.;T;.;.

Sift4G

Benign

0.92

T;T;.;.;T;.

Polyphen

0.0

.;.;B;.;.;.

Vest4

0.088

MVP

0.072

ClinPred

0.030

GERP RS

-2.1

PromoterAI

0.0038

Neutral

(source)

Varity_R

0.055

gMVP

0.18

Mutation Taster

=133/67

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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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rs368034599

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