rs10484558

Positions:

• chr6-31647737-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001387994.1(BAG6):​c.642A>G​(p.Thr214=) 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAG6	NM_001387994.1	c.642A>G	p.Thr214=	synonymous_variant	7/26	ENST00000676615.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAG6	ENST00000676615.2	c.642A>G	p.Thr214=	synonymous_variant	7/26		NM_001387994.1	A2

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

GnomAD3 exomes AF: 0.0339 AC: 8031 AN: 237004 Hom.: 321 AF XY: 0.0308 AC XY: 3994 AN XY: 129712

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 SAS exome AF: 0.0156

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

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.0532

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.0452

Gnomad4 SAS exome AF: 0.0162

Gnomad4 FIN exome AF: 0.00277

Gnomad4 NFE exome AF: 0.0182

Gnomad4 OTH exome AF: 0.0381

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

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0574

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.0170

Gnomad4 SAS AF: 0.0176

Gnomad4 FIN AF: 0.00198

Gnomad4 NFE AF: 0.0220

Gnomad4 OTH AF: 0.0742

Alfa AF: 0.0381 Hom.: 208

Bravo AF: 0.0590

Asia WGS AF: 0.0270 AC: 93 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.3
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9

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: rs10484558; hg19: chr6-31615514; COSMIC: COSV52995515; COSMIC: COSV52995515;