rs1043782

chr8-38210806-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.510

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
BAG4	NM_004874.4	c.*313C>T		3_prime_UTR_variant	5/5	ENST00000287322.5
BAG4	NM_001204878.2	c.*313C>T		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAG4	ENST00000287322.5	c.*313C>T		3_prime_UTR_variant	5/5	1	NM_004874.4	P1
BAG4	ENST00000432471.6	c.*313C>T		3_prime_UTR_variant	4/4	1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36711 AN: 151986 Hom.: 4598 Cov.: 32

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.: 2 AF XY: 0.227 AC XY: 6799 AN XY: 29924

Gnomad4 AFR exome AF: 0.273

Gnomad4 AMR exome AF: 0.260

Gnomad4 ASJ exome AF: 0.170

Gnomad4 EAS exome AF: 0.307

Gnomad4 SAS exome AF: 0.122

Gnomad4 FIN exome AF: 0.187

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.233

GnomAD4 genome AF: 0.242 AC: 36771 AN: 152104 Hom.: 4612 Cov.: 32 AF XY: 0.236 AC XY: 17544 AN XY: 74354

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.239

Alfa AF: 0.245 Hom.: 1300

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
Dann	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1043782; hg19: chr8-38068324;