rs755714

Variant names:

• chr6-31642036-C-T
• rs755714
• NM_001387994.1:c.2335+76G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 33 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 -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 rank	MANE	Protein	UniProt
BAG6	NM_001387994.1	c.2335+76G>A		intron_variant	Intron 16 of 25	ENST00000676615.2	NP_001374923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAG6	ENST00000676615.2	c.2335+76G>A		intron_variant	Intron 16 of 25		NM_001387994.1	ENSP00000502941.1

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

African (AFR) AF: 0.0426 AC: 1404 AN: 32966

American (AMR) AF: 0.375 AC: 16241 AN: 43282

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 11861 AN: 24508

East Asian (EAS) AF: 0.418 AC: 16486 AN: 39426

South Asian (SAS) AF: 0.308 AC: 25537 AN: 83002

European-Finnish (FIN) AF: 0.281 AC: 14500 AN: 51518

Middle Eastern (MID) AF: 0.390 AC: 2209 AN: 5658

European-Non Finnish (NFE) AF: 0.296 AC: 325021 AN: 1098662

Other (OTH) AF: 0.291 AC: 17255 AN: 59314

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

African (AFR) AF: 0.0539 AC: 2239 AN: 41512

American (AMR) AF: 0.302 AC: 4619 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1685 AN: 3464

East Asian (EAS) AF: 0.360 AC: 1856 AN: 5152

South Asian (SAS) AF: 0.313 AC: 1510 AN: 4818

European-Finnish (FIN) AF: 0.283 AC: 2983 AN: 10550

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20658 AN: 67918

Other (OTH) AF: 0.266 AC: 561 AN: 2110

Alfa AF: 0.284 Hom.: 19299

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
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs755714; hg19: chr6-31609813;