rs743400

chr6-31639334-A-Gchr6-31639334-A-T

Variant summary

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

The NM_001387994.1(BAG6):c.3394-108T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0615 in 1,434,778 control chromosomes in the GnomAD database, including 3,534 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 0.077 (649 hom., cov: 32)
  • Exomes 𝑓: 0.060 (2885 hom.)
• Consequence: BAG6 NM_001387994.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAG6	NM_001387994.1	c.3394-108T>C		intron_variant		ENST00000676615.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAG6	ENST00000676615.2	c.3394-108T>C		intron_variant			NM_001387994.1	A2

Frequencies

GnomAD3 genomes AF: 0.0767 AC: 11658 AN: 151980 Hom.: 648 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0972

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.00643

Gnomad FIN AF: 0.00482

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0582

Gnomad OTH AF: 0.0833

GnomAD4 exome AF: 0.0597 AC: 76578 AN: 1282680 Hom.: 2885 Cov.: 19 AF XY: 0.0571 AC XY: 36519 AN XY: 639432

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.0671

Gnomad4 ASJ exome AF: 0.0412

Gnomad4 EAS exome AF: 0.000908

Gnomad4 SAS exome AF: 0.00851

Gnomad4 FIN exome AF: 0.00776

Gnomad4 NFE exome AF: 0.0668

Gnomad4 OTH exome AF: 0.0583

GnomAD4 genome AF: 0.0766 AC: 11656 AN: 152098 Hom.: 649 Cov.: 32 AF XY: 0.0728 AC XY: 5414 AN XY: 74358

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.0971

Gnomad4 ASJ AF: 0.0435

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.00623

Gnomad4 FIN AF: 0.00482

Gnomad4 NFE AF: 0.0582

Gnomad4 OTH AF: 0.0820

Alfa AF: 0.0586 Hom.: 232

Bravo AF: 0.0888

Asia WGS AF: 0.0110 AC: 39 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	7.5
Dann	Benign	0.74

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: rs743400; hg19: chr6-31607111;