dbSNP rs1043782: BAG4:c.*313C>T (chr8-38210806-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004874.4(BAG4):c.*313C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 210,424 control chromosomes in the GnomAD database, including 6,247 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 4612 hom., cov: 32)

Exomes 𝑓: 0.23 ( 1635 hom. )

Consequence

BAG4
NM_004874.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.510

Publications

16 publications found

Variant links:

Genes affected

BAG4 (HGNC:940): (BAG cochaperone 4) The protein encoded by this gene is a member of the BAG1-related protein family. BAG1 is an anti-apoptotic protein that functions through interactions with a variety of cell apoptosis and growth related proteins including BCL-2, Raf-protein kinase, steroid hormone receptors, growth factor receptors and members of the heat shock protein 70 kDa family. This protein contains a BAG domain near the C-terminus, which could bind and inhibit the chaperone activity of Hsc70/Hsp70. This protein was found to be associated with the death domain of tumor necrosis factor receptor type 1 (TNF-R1) and death receptor-3 (DR3), and thereby negatively regulates downstream cell death signaling. The regulatory role of this protein in cell death was demonstrated in epithelial cells which undergo apoptosis while integrin mediated matrix contacts are lost. Alternatively spliced transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Mar 2011]

BAG4 links:

ENSG00000285632 (HGNC:):

ENSG00000285632 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAG4	NM_004874.4 link	c.*313C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000287322.5	NP_004865.1	O95429-1
BAG4	NM_001204878.2 link	c.*313C>T		3_prime_UTR_variant	Exon 4 of 4		NP_001191807.1	O95429-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
BAG4	ENST00000287322.5 link	c.*313C>T	3_prime_UTR_variant	Exon 5 of 5	1	NM_004874.4	ENSP00000287322.4	O95429-1
BAG4	ENST00000432471.6 link	c.*313C>T	3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000393298.2	O95429-2
ENSG00000285632	ENST00000720731.1 link	n.83-343G>A	intron_variant	Intron 1 of 3
ENSG00000285632	ENST00000720732.1 link	n.112-343G>A	intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes

AF:

0.242

AC:

36711

AN:

151986

Hom.:

4598

Cov.:

show subpopulations

Gnomad AFR

AF:

0.259

Gnomad AMI

AF:

0.359

Gnomad AMR

AF:

0.248

Gnomad ASJ

AF:

0.167

Gnomad EAS

AF:

0.308

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.194

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.243

Gnomad OTH

AF:

0.240

GnomAD4 exome

AF:

0.232

AC:

13532

AN:

58320

Hom.:

1635

Cov.:

AF XY:

0.227

AC XY:

6799

AN XY:

29924

show subpopulations

African (AFR)

AF:

0.273

AC:

374

AN:

1370

American (AMR)

AF:

0.260

AC:

898

AN:

3454

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

325

AN:

1914

East Asian (EAS)

AF:

0.307

AC:

1058

AN:

3448

South Asian (SAS)

AF:

0.122

AC:

524

AN:

4286

European-Finnish (FIN)

AF:

0.187

AC:

491

AN:

2622

Middle Eastern (MID)

AF:

0.196

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.240

AC:

9006

AN:

37522

Other (OTH)

AF:

0.233

AC:

814

AN:

3490

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

520

1040

1559

2079

2599

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<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:

0.242

AC:

36771

AN:

152104

Hom.:

4612

Cov.:

AF XY:

0.236

AC XY:

17544

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.259

AC:

10768

AN:

41516

American (AMR)

AF:

0.248

AC:

3789

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

578

AN:

3470

East Asian (EAS)

AF:

0.308

AC:

1590

AN:

5166

South Asian (SAS)

AF:

0.116

AC:

560

AN:

4826

European-Finnish (FIN)

AF:

0.194

AC:

2050

AN:

10582

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.243

AC:

16536

AN:

67960

Other (OTH)

AF:

0.239

AC:

504

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1419

2837

4256

5674

7093

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

372

744

1116

1488

1860

<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:

0.244

Hom.:

1455

Bravo

AF:

0.253

Asia WGS

AF:

0.212

AC:

736

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.0

(source)

DANN

Benign

0.43

PhyloP100

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

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

Computational scores

Splicing

Publications

Other links and lift over