chr6-31639644-C-T

Variant names:

• chr6-31639644-C-T
• rs148136430
• NM_001387994.1:c.3249G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001387994.1(BAG6):​c.3249G>A​(p.Thr1083Thr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000706 in 1,607,742 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (4 hom.)
• Consequence: BAG6 NM_001387994.1 splice_region, synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.122
• Publications: 0 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 6-31639644-C-T is Benign according to our data. Variant chr6-31639644-C-T is described in ClinVar as Benign. ClinVar VariationId is 724730.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.122 with no splicing effect.
• BS2: High AC in GnomAd4 at 486 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAG6	NM_001387994.1	MANE Select	c.3249G>A	p.Thr1083Thr	splice_region synonymous	Exon 25 of 26	NP_001374923.1	P46379-3
	BAG6	NM_001388012.1		c.3276G>A	p.Thr1092Thr	splice_region synonymous	Exon 25 of 26	NP_001374941.1
	BAG6	NM_001387989.1		c.3249G>A	p.Thr1083Thr	splice_region synonymous	Exon 25 of 26	NP_001374918.1	P46379-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAG6	ENST00000676615.2	MANE Select	c.3249G>A	p.Thr1083Thr	splice_region synonymous	Exon 25 of 26	ENSP00000502941.1	P46379-3
	BAG6	ENST00000211379.9	TSL:1	c.3141G>A	p.Thr1047Thr	splice_region synonymous	Exon 24 of 25	ENSP00000211379.5	P46379-2
	BAG6	ENST00000375976.8	TSL:1	c.3141G>A	p.Thr1047Thr	splice_region synonymous	Exon 24 of 25	ENSP00000365143.4	P46379-2

Frequencies

GnomAD3 genomes AF: 0.00319 AC: 485 AN: 152144 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00978

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00367

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00384

GnomAD2 exomes AF: 0.00108 AC: 263 AN: 244188 AF XY: 0.00104

Gnomad AFR exome AF: 0.00970

Gnomad AMR exome AF: 0.000684

Gnomad ASJ exome AF: 0.000309

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000290

Gnomad OTH exome AF: 0.00101

GnomAD4 exome AF: 0.000446 AC: 649 AN: 1455480 Hom.: 4 Cov.: 31 AF XY: 0.000518 AC XY: 375 AN XY: 723364

African (AFR) AF: 0.00784 AC: 261 AN: 33294

American (AMR) AF: 0.00112 AC: 49 AN: 43908

Ashkenazi Jewish (ASJ) AF: 0.0000386 AC: 1 AN: 25892

East Asian (EAS) AF: 0.00 AC: 0 AN: 39562

South Asian (SAS) AF: 0.00224 AC: 192 AN: 85814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53294

Middle Eastern (MID) AF: 0.00182 AC: 10 AN: 5484

European-Non Finnish (NFE) AF: 0.0000749 AC: 83 AN: 1108194

Other (OTH) AF: 0.000883 AC: 53 AN: 60038

GnomAD4 genome AF: 0.00319 AC: 486 AN: 152262 Hom.: 3 Cov.: 32 AF XY: 0.00298 AC XY: 222 AN XY: 74438

African (AFR) AF: 0.00977 AC: 406 AN: 41536

American (AMR) AF: 0.00366 AC: 56 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68032

Other (OTH) AF: 0.00380 AC: 8 AN: 2108

Alfa AF: 0.00101 Hom.: 0

Bravo AF: 0.00388

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000652

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.7
DANN	Benign	0.89
PhyloP100		-0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs148136430; hg19: chr6-31607421;