rs755714

chr6-31642036-C-T

Variant summary

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

The NM_001387994.1(BAG6):c.2335+76G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 1,590,352 control chromosomes in the GnomAD database, including 73,234 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 (5582 hom., cov: 31)
  • Exomes 𝑓: 0.30 (67652 hom.)
• Consequence: BAG6 NM_001387994.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.723

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAG6	NM_001387994.1	c.2335+76G>A		intron_variant		ENST00000676615.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAG6	ENST00000676615.2	c.2335+76G>A		intron_variant			NM_001387994.1	A2

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36530 AN: 151898 Hom.: 5580 Cov.: 31

Gnomad AFR AF: 0.0540

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.267

GnomAD4 exome AF: 0.299 AC: 430514 AN: 1438336 Hom.: 67652 Cov.: 61 AF XY: 0.303 AC XY: 215667 AN XY: 712556

Gnomad4 AFR exome AF: 0.0426

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.484

Gnomad4 EAS exome AF: 0.418

Gnomad4 SAS exome AF: 0.308

Gnomad4 FIN exome AF: 0.281

Gnomad4 NFE exome AF: 0.296

Gnomad4 OTH exome AF: 0.291

GnomAD4 genome AF: 0.240 AC: 36538 AN: 152016 Hom.: 5582 Cov.: 31 AF XY: 0.243 AC XY: 18075 AN XY: 74290

Gnomad4 AFR AF: 0.0539

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.266

Alfa AF: 0.297 Hom.: 4835

Bravo AF: 0.234

Asia WGS AF: 0.300 AC: 1047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	8.2
Dann	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs755714; hg19: chr6-31609813;