rs805303

Positions:

• chr6-31648589-G-A
• chr6-31648589-G-C

Variant summary

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

The NM_001387994.1(BAG6):​c.552+88C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,298,384 control chromosomes in the GnomAD database, including 100,027 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 0.44 (15683 hom., cov: 31)
  • Exomes 𝑓: 0.38 (84344 hom.)
• Consequence: BAG6 NM_001387994.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAG6	NM_001387994.1	c.552+88C>T		intron_variant		ENST00000676615.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAG6	ENST00000676615.2	c.552+88C>T		intron_variant			NM_001387994.1	A2

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67418 AN: 151802 Hom.: 15668 Cov.: 31

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.431

GnomAD4 exome AF: 0.378 AC: 433619 AN: 1146464 Hom.: 84344 AF XY: 0.372 AC XY: 214941 AN XY: 578074

Gnomad4 AFR exome AF: 0.603

Gnomad4 AMR exome AF: 0.429

Gnomad4 ASJ exome AF: 0.341

Gnomad4 EAS exome AF: 0.414

Gnomad4 SAS exome AF: 0.288

Gnomad4 FIN exome AF: 0.481

Gnomad4 NFE exome AF: 0.370

Gnomad4 OTH exome AF: 0.385

GnomAD4 genome AF: 0.444 AC: 67474 AN: 151920 Hom.: 15683 Cov.: 31 AF XY: 0.446 AC XY: 33116 AN XY: 74250

Gnomad4 AFR AF: 0.592

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.430

Alfa AF: 0.375 Hom.: 19086

Bravo AF: 0.449

Asia WGS AF: 0.363 AC: 1262 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	3.0
DANN	Benign	0.29

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: rs805303; hg19: chr6-31616366; COSMIC: COSV52993747; COSMIC: COSV52993747;