rs3130048

Variant names:

• chr6-31645962-T-C
• rs3130048
• NM_001387994.1:c.919-358A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387994.1(BAG6):​c.919-358A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,100 control chromosomes in the GnomAD database, including 4,419 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 0.23 (4419 hom., cov: 32)
• Consequence: BAG6 NM_001387994.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.899
• Publications: 39 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAG6	NM_001387994.1	c.919-358A>G		intron_variant	Intron 8 of 25	ENST00000676615.2	NP_001374923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAG6	ENST00000676615.2	c.919-358A>G		intron_variant	Intron 8 of 25		NM_001387994.1	ENSP00000502941.1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35456 AN: 151982 Hom.: 4420 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.215

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.233 AC: 35453 AN: 152100 Hom.: 4419 Cov.: 32 AF XY: 0.230 AC XY: 17081 AN XY: 74354

African (AFR) AF: 0.207 AC: 8604 AN: 41500

American (AMR) AF: 0.149 AC: 2282 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 657 AN: 3464

East Asian (EAS) AF: 0.295 AC: 1518 AN: 5154

South Asian (SAS) AF: 0.268 AC: 1295 AN: 4826

European-Finnish (FIN) AF: 0.203 AC: 2142 AN: 10568

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18118 AN: 67984

Other (OTH) AF: 0.215 AC: 454 AN: 2114

Alfa AF: 0.251 Hom.: 8693

Bravo AF: 0.227

Asia WGS AF: 0.224 AC: 776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.66
PhyloP100		-0.90
PromoterAI		-0.0034	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3130048; hg19: chr6-31613739;