6-31641495-T-C

Variant names:

• chr6-31641495-T-C
• rs3130628
• NM_001387994.1:c.2559+44A>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.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
• Publications: 36 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387994.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAG6	NM_001387994.1	MANE Select	c.2559+44A>G		intron	N/A	NP_001374923.1
	BAG6	NM_001388012.1		c.2586+44A>G		intron	N/A	NP_001374941.1
	BAG6	NM_001387989.1		c.2559+44A>G		intron	N/A	NP_001374918.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAG6	ENST00000676615.2	MANE Select	c.2559+44A>G		intron	N/A	ENSP00000502941.1
	BAG6	ENST00000211379.9	TSL:1	c.2451+44A>G		intron	N/A	ENSP00000211379.5
	BAG6	ENST00000375976.8	TSL:1	c.2451+44A>G		intron	N/A	ENSP00000365143.4

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

GnomAD2 exomes AF: 0.148 AC: 37089 AN: 251378 AF XY: 0.147

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 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

African (AFR) AF: 0.231 AC: 7740 AN: 33476

American (AMR) AF: 0.0825 AC: 3688 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 3112 AN: 26136

East Asian (EAS) AF: 0.0466 AC: 1850 AN: 39696

South Asian (SAS) AF: 0.115 AC: 9914 AN: 86254

European-Finnish (FIN) AF: 0.160 AC: 8556 AN: 53412

Middle Eastern (MID) AF: 0.0924 AC: 533 AN: 5768

European-Non Finnish (NFE) AF: 0.192 AC: 213581 AN: 1111862

Other (OTH) AF: 0.167 AC: 10065 AN: 60386

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

African (AFR) AF: 0.219 AC: 9093 AN: 41504

American (AMR) AF: 0.101 AC: 1545 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 399 AN: 3470

East Asian (EAS) AF: 0.0788 AC: 409 AN: 5188

South Asian (SAS) AF: 0.125 AC: 603 AN: 4822

European-Finnish (FIN) AF: 0.162 AC: 1714 AN: 10598

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12538 AN: 67994

Other (OTH) AF: 0.154 AC: 326 AN: 2114

Alfa AF: 0.186 Hom.: 7355

Bravo AF: 0.175

Asia WGS AF: 0.0980 AC: 341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.7
DANN	Benign	0.56
PhyloP100		-0.52
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
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: rs3130628; hg19: chr6-31609272;