6-57173571-A-C

Variant names:

• chr6-57173571-A-C
• rs9370567
• NM_004282.4:c.113+761A>C

Variant summary

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

The NM_004282.4(BAG2):​c.113+761A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0786 in 853,372 control chromosomes in the GnomAD database, including 2,792 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 0.089 (673 hom., cov: 32)
  • Exomes 𝑓: 0.076 (2119 hom.)
• Consequence: BAG2 NM_004282.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.523
• Publications: 4 publications found

Genes affected

BAG2 (HGNC:938): (BAG cochaperone 2) BAG proteins compete with Hip for binding to the Hsc70/Hsp70 ATPase domain and promote substrate release. All the BAG proteins have an approximately 45-amino acid BAG domain near the C terminus but differ markedly in their N-terminal regions. The predicted BAG2 protein contains 211 amino acids. The BAG domains of BAG1, BAG2, and BAG3 interact specifically with the Hsc70 ATPase domain in vitro and in mammalian cells. All 3 proteins bind with high affinity to the ATPase domain of Hsc70 and inhibit its chaperone activity in a Hip-repressible manner. [provided by RefSeq, Jul 2008]

ZNF451-AS1 (HGNC:53824): (ZNF451 regulatory antisense RNA 1)

ENSG00000307695 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAG2	NM_004282.4	c.113+761A>C		intron_variant	Intron 1 of 2	ENST00000370693.5	NP_004273.1
BAG2	XM_005249490.5	c.-180+110A>C		intron_variant	Intron 1 of 3		XP_005249547.1
BAG2	XM_011514999.4	c.-92+110A>C		intron_variant	Intron 1 of 3		XP_011513301.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAG2	ENST00000370693.5	c.113+761A>C		intron_variant	Intron 1 of 2	1	NM_004282.4	ENSP00000359727.4
ZNF451-AS1	ENST00000585414.1	n.501-91T>G		intron_variant	Intron 1 of 2	5
ENSG00000307695	ENST00000827921.1	n.547+110A>C		intron_variant	Intron 1 of 1
ZNF451-AS1	ENST00000592785.6	n.-144T>G		upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0891 AC: 13559 AN: 152150 Hom.: 673 Cov.: 32

Gnomad AFR AF: 0.0901

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0776

Gnomad ASJ AF: 0.0377

Gnomad EAS AF: 0.0946

Gnomad SAS AF: 0.0792

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0823

Gnomad OTH AF: 0.0793

GnomAD4 exome AF: 0.0763 AC: 53487 AN: 701104 Hom.: 2119 Cov.: 9 AF XY: 0.0761 AC XY: 24803 AN XY: 325902

African (AFR) AF: 0.0782 AC: 1008 AN: 12882

American (AMR) AF: 0.0898 AC: 74 AN: 824

Ashkenazi Jewish (ASJ) AF: 0.0358 AC: 157 AN: 4380

East Asian (EAS) AF: 0.0929 AC: 277 AN: 2982

South Asian (SAS) AF: 0.0702 AC: 959 AN: 13660

European-Finnish (FIN) AF: 0.130 AC: 28 AN: 216

Middle Eastern (MID) AF: 0.0355 AC: 49 AN: 1382

European-Non Finnish (NFE) AF: 0.0768 AC: 49274 AN: 641810

Other (OTH) AF: 0.0723 AC: 1661 AN: 22968

GnomAD4 genome AF: 0.0892 AC: 13581 AN: 152268 Hom.: 673 Cov.: 32 AF XY: 0.0912 AC XY: 6790 AN XY: 74458

African (AFR) AF: 0.0902 AC: 3747 AN: 41536

American (AMR) AF: 0.0778 AC: 1191 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0377 AC: 131 AN: 3472

East Asian (EAS) AF: 0.0948 AC: 492 AN: 5188

South Asian (SAS) AF: 0.0793 AC: 383 AN: 4830

European-Finnish (FIN) AF: 0.172 AC: 1828 AN: 10598

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0823 AC: 5600 AN: 68024

Other (OTH) AF: 0.0799 AC: 169 AN: 2114

Alfa AF: 0.0552 Hom.: 61

Bravo AF: 0.0821

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	-0.81
CADD	Benign	2.9
DANN	Benign	0.62
PhyloP100		-0.52
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: rs9370567; hg19: chr6-57038369;