chr8-38205717-C-A

Variant names:

• chr8-38205717-C-A
• rs7836805
• NM_004874.4:c.379-1795C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004874.4(BAG4):​c.379-1795C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 151,880 control chromosomes in the GnomAD database, including 4,517 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 (4517 hom., cov: 30)
• Consequence: BAG4 NM_004874.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0200
• Publications: 20 publications found

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]

ENSG00000285632 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• 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	c.379-1795C>A		intron_variant	Intron 2 of 4	ENST00000287322.5	NP_004865.1
BAG4	NM_001204878.2	c.271-1795C>A		intron_variant	Intron 1 of 3		NP_001191807.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAG4	ENST00000287322.5	c.379-1795C>A		intron_variant	Intron 2 of 4	1	NM_004874.4	ENSP00000287322.4

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36308 AN: 151762 Hom.: 4505 Cov.: 30

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.238

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.239 AC: 36361 AN: 151880 Hom.: 4517 Cov.: 30 AF XY: 0.234 AC XY: 17365 AN XY: 74210

African (AFR) AF: 0.251 AC: 10410 AN: 41422

American (AMR) AF: 0.247 AC: 3768 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 577 AN: 3470

East Asian (EAS) AF: 0.308 AC: 1585 AN: 5150

South Asian (SAS) AF: 0.117 AC: 561 AN: 4812

European-Finnish (FIN) AF: 0.193 AC: 2032 AN: 10526

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16532 AN: 67958

Other (OTH) AF: 0.237 AC: 500 AN: 2106

Alfa AF: 0.240 Hom.: 18390

Bravo AF: 0.250

Asia WGS AF: 0.211 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.61
PhyloP100		-0.020
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7836805; hg19: chr8-38063235;