rs762370493

Variant names:

• chr8-38207558-C-A
• rs762370493
• NM_004874.4:c.425C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-38207558-C-A
• chr8-38207558-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004874.4(BAG4):​c.425C>A​(p.Pro142Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P142R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: BAG4 NM_004874.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.74
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23989955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAG4	NM_004874.4	c.425C>A	p.Pro142Gln	missense_variant	Exon 3 of 5	ENST00000287322.5	NP_004865.1
BAG4	NM_001204878.2	c.317C>A	p.Pro106Gln	missense_variant	Exon 2 of 4		NP_001191807.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAG4	ENST00000287322.5	c.425C>A	p.Pro142Gln	missense_variant	Exon 3 of 5	1	NM_004874.4	ENSP00000287322.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.0034	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	.;T
Eigen	Benign	0.13
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	1.9	.;L
PhyloP100		4.7
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.66	N;N
REVEL	Benign	0.25
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.016	D;T
Polyphen		0.95	.;P
Vest4		0.35
MutPred		0.36		.;Loss of glycosylation at P142 (P = 0.0205);
MVP		0.88
MPC		0.098
ClinPred		0.85	D
GERP RS		5.2
PromoterAI		0.00060	Neutral
Varity_R		0.11
gMVP		0.31
Mutation Taster		=79/21	polymorphism

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: rs762370493; hg19: chr8-38065076;