rs3130628

Positions:

• chr6-31641495-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.2559+44A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,613,898 control chromosomes in the GnomAD database, including 27,216 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 0.18 (2602 hom., cov: 32)
  • Exomes 𝑓: 0.18 (24614 hom.)
• Consequence: BAG6 NM_001387994.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.519

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BAG6	NM_001387994.1	c.2559+44A>G		intron_variant		ENST00000676615.2	NP_001374923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAG6	ENST00000676615.2	c.2559+44A>G		intron_variant			NM_001387994.1	ENSP00000502941	A2

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26833 AN: 152066 Hom.: 2602 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0783

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.156

GnomAD3 exomes AF: 0.148 AC: 37089 AN: 251378 Hom.: 3124 AF XY: 0.147 AC XY: 19948 AN XY: 135872

Gnomad AFR exome AF: 0.226

Gnomad AMR exome AF: 0.0782

Gnomad ASJ exome AF: 0.114

Gnomad EAS exome AF: 0.0961

Gnomad SAS exome AF: 0.109

Gnomad FIN exome AF: 0.159

Gnomad NFE exome AF: 0.177

Gnomad OTH exome AF: 0.141

GnomAD4 exome AF: 0.177 AC: 259039 AN: 1461714 Hom.: 24614 Cov.: 36 AF XY: 0.175 AC XY: 127029 AN XY: 727170

Gnomad4 AFR exome AF: 0.231

Gnomad4 AMR exome AF: 0.0825

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.0466

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.176 AC: 26837 AN: 152184 Hom.: 2602 Cov.: 32 AF XY: 0.171 AC XY: 12740 AN XY: 74408

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.0788

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.154

Alfa AF: 0.178 Hom.: 2090

Bravo AF: 0.175

Asia WGS AF: 0.0980 AC: 341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.7
DANN	Benign	0.56
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1

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: rs3130628; hg19: chr6-31609272;