rs9370567

chr6-57173571-A-Cchr6-57173571-A-G

Variant summary

Our verdict is Benign. Variant got -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

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)

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
BAG2	NM_004282.4	c.113+761A>C		intron_variant		ENST00000370693.5
BAG2	XM_005249490.5	c.-180+110A>C		intron_variant
BAG2	XM_011514999.4	c.-92+110A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAG2	ENST00000370693.5	c.113+761A>C		intron_variant		1	NM_004282.4	P1
ZNF451-AS1	ENST00000585414.1	n.501-91T>G		intron_variant, non_coding_transcript_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

Gnomad4 AFR exome AF: 0.0782

Gnomad4 AMR exome AF: 0.0898

Gnomad4 ASJ exome AF: 0.0358

Gnomad4 EAS exome AF: 0.0929

Gnomad4 SAS exome AF: 0.0702

Gnomad4 FIN exome AF: 0.130

Gnomad4 NFE exome AF: 0.0768

Gnomad4 OTH exome AF: 0.0723

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

Gnomad4 AFR AF: 0.0902

Gnomad4 AMR AF: 0.0778

Gnomad4 ASJ AF: 0.0377

Gnomad4 EAS AF: 0.0948

Gnomad4 SAS AF: 0.0793

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.0823

Gnomad4 OTH AF: 0.0799

Alfa AF: 0.0540 Hom.: 58

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

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: rs9370567; hg19: chr6-57038369;