6-31644000-T-C

Variant summary

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

The NM_001387994.1(BAG6):c.1669-23A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 1,613,678 control chromosomes in the GnomAD database, including 550,293 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 0.81 (49963 hom., cov: 31)
  • Exomes 𝑓: 0.83 (500330 hom.)
• Consequence: BAG6 NM_001387994.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAG6	NM_001387994.1	c.1669-23A>G		intron_variant		ENST00000676615.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAG6	ENST00000676615.2	c.1669-23A>G		intron_variant			NM_001387994.1	A2

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122901 AN: 151980 Hom.: 49908 Cov.: 31

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.815

GnomAD3 exomes AF: 0.838 AC: 209298 AN: 249740 Hom.: 88064 AF XY: 0.837 AC XY: 113246 AN XY: 135242

Gnomad AFR exome AF: 0.728

Gnomad AMR exome AF: 0.874

Gnomad ASJ exome AF: 0.909

Gnomad EAS exome AF: 0.848

Gnomad SAS exome AF: 0.822

Gnomad FIN exome AF: 0.863

Gnomad NFE exome AF: 0.834

Gnomad OTH exome AF: 0.839

GnomAD4 exome AF: 0.826 AC: 1207749 AN: 1461580 Hom.: 500330 Cov.: 47 AF XY: 0.827 AC XY: 601090 AN XY: 727116

Gnomad4 AFR exome AF: 0.727

Gnomad4 AMR exome AF: 0.870

Gnomad4 ASJ exome AF: 0.904

Gnomad4 EAS exome AF: 0.890

Gnomad4 SAS exome AF: 0.823

Gnomad4 FIN exome AF: 0.858

Gnomad4 NFE exome AF: 0.823

Gnomad4 OTH exome AF: 0.820

GnomAD4 genome AF: 0.809 AC: 123013 AN: 152098 Hom.: 49963 Cov.: 31 AF XY: 0.810 AC XY: 60250 AN XY: 74346

Gnomad4 AFR AF: 0.729

Gnomad4 AMR AF: 0.846

Gnomad4 ASJ AF: 0.901

Gnomad4 EAS AF: 0.854

Gnomad4 SAS AF: 0.837

Gnomad4 FIN AF: 0.870

Gnomad4 NFE AF: 0.827

Gnomad4 OTH AF: 0.816

Alfa AF: 0.833 Hom.: 79774

Bravo AF: 0.805

Asia WGS AF: 0.870 AC: 3026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.31
Dann	Benign	0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs760293; hg19: chr6-31611777;