chr6-31647737-T-C

Variant names:

• chr6-31647737-T-C
• rs10484558
• NM_001387994.1:c.642A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001387994.1(BAG6):​c.642A>G​(p.Thr214Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 1,604,910 control chromosomes in the GnomAD database, including 1,326 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 0.052 (365 hom., cov: 31)
  • Exomes 𝑓: 0.025 (961 hom.)
• Consequence: BAG6 NM_001387994.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107
• Publications: 19 publications found

Genes affected

BAG6 (HGNC:13919): (BAG cochaperone 6) This gene was first characterized as part of a cluster of genes located within the human major histocompatibility complex class III region. This gene encodes a nuclear protein that is cleaved by caspase 3 and is implicated in the control of apoptosis. In addition, the protein forms a complex with E1A binding protein p300 and is required for the acetylation of p53 in response to DNA damage. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-0.107 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387994.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAG6	NM_001387994.1	MANE Select	c.642A>G	p.Thr214Thr	synonymous	Exon 7 of 26	NP_001374923.1
	BAG6	NM_001388012.1		c.642A>G	p.Thr214Thr	synonymous	Exon 7 of 26	NP_001374941.1
	BAG6	NM_001387989.1		c.642A>G	p.Thr214Thr	synonymous	Exon 7 of 26	NP_001374918.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAG6	ENST00000676615.2	MANE Select	c.642A>G	p.Thr214Thr	synonymous	Exon 7 of 26	ENSP00000502941.1
	BAG6	ENST00000211379.9	TSL:1	c.642A>G	p.Thr214Thr	synonymous	Exon 7 of 25	ENSP00000211379.5
	BAG6	ENST00000375976.8	TSL:1	c.642A>G	p.Thr214Thr	synonymous	Exon 7 of 25	ENSP00000365143.4

Frequencies

GnomAD3 genomes AF: 0.0515 AC: 7826 AN: 152104 Hom.: 361 Cov.: 31

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0574

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0169

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0220

Gnomad OTH AF: 0.0750

GnomAD2 exomes AF: 0.0339 AC: 8031 AN: 237004 AF XY: 0.0308

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.0521

Gnomad ASJ exome AF: 0.139

Gnomad EAS exome AF: 0.0136

Gnomad FIN exome AF: 0.00265

Gnomad NFE exome AF: 0.0221

Gnomad OTH exome AF: 0.0463

GnomAD4 exome AF: 0.0245 AC: 35625 AN: 1452688 Hom.: 961 Cov.: 32 AF XY: 0.0243 AC XY: 17529 AN XY: 722836

African (AFR) AF: 0.110 AC: 3625 AN: 32856

American (AMR) AF: 0.0532 AC: 2265 AN: 42572

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 3604 AN: 25854

East Asian (EAS) AF: 0.0452 AC: 1772 AN: 39184

South Asian (SAS) AF: 0.0162 AC: 1376 AN: 85038

European-Finnish (FIN) AF: 0.00277 AC: 145 AN: 52298

Middle Eastern (MID) AF: 0.0681 AC: 391 AN: 5742

European-Non Finnish (NFE) AF: 0.0182 AC: 20160 AN: 1109060

Other (OTH) AF: 0.0381 AC: 2287 AN: 60084

GnomAD4 genome AF: 0.0516 AC: 7849 AN: 152222 Hom.: 365 Cov.: 31 AF XY: 0.0496 AC XY: 3693 AN XY: 74436

African (AFR) AF: 0.111 AC: 4614 AN: 41504

American (AMR) AF: 0.0574 AC: 878 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3472

East Asian (EAS) AF: 0.0170 AC: 88 AN: 5180

South Asian (SAS) AF: 0.0176 AC: 85 AN: 4826

European-Finnish (FIN) AF: 0.00198 AC: 21 AN: 10612

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0220 AC: 1497 AN: 68018

Other (OTH) AF: 0.0742 AC: 157 AN: 2116

Alfa AF: 0.0372 Hom.: 539

Bravo AF: 0.0590

Asia WGS AF: 0.0270 AC: 93 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.3
DANN	Benign	0.61
PhyloP100		-0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
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: rs10484558; hg19: chr6-31615514; COSMIC: COSV52995515; COSMIC: COSV52995515;