chr8-38205717-C-A

Position:

• chr8-38205717-C-A

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
BAG4	NM_004874.4	c.379-1795C>A		intron_variant		ENST00000287322.5	NP_004865.1
BAG4	NM_001204878.2	c.271-1795C>A		intron_variant			NP_001191807.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAG4	ENST00000287322.5	c.379-1795C>A		intron_variant		1	NM_004874.4	ENSP00000287322.4
BAG4	ENST00000432471.6	c.271-1795C>A		intron_variant		1		ENSP00000393298.2
BAG4	ENST00000521282.1	n.301-1795C>A		intron_variant		2

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

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.237

Alfa AF: 0.239 Hom.: 8739

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

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

Other links and lift over

dbSNP: rs7836805; hg19: chr8-38063235;