rs7948948

chr11-123057467-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The 11-123057467-A-G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 335,620 control chromosomes in the GnomAD database, including 8,140 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 (4911 hom., cov: 32)
  • Exomes 𝑓: 0.17 (3229 hom.)
• Consequence: HSPA8 NM_006597.6 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.408

Genes affected

HSPA8 (HGNC:5241): (heat shock protein family A (Hsp70) member 8) This gene encodes a member of the heat shock protein 70 family, which contains both heat-inducible and constitutively expressed members. This protein belongs to the latter group, which are also referred to as heat-shock cognate proteins. It functions as a chaperone, and binds to nascent polypeptides to facilitate correct folding. It also functions as an ATPase in the disassembly of clathrin-coated vesicles during transport of membrane components through the cell. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA8	NM_006597.6			downstream_gene_variant		ENST00000534624.6
HSPA8	NM_153201.4			downstream_gene_variant
HSPA8	XM_011542798.2			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA8	ENST00000534624.6			downstream_gene_variant		1	NM_006597.6	P1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34993 AN: 152062 Hom.: 4891 Cov.: 32

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0881

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.206

GnomAD4 exome AF: 0.175 AC: 32086 AN: 183440 Hom.: 3229 Cov.: 0 AF XY: 0.177 AC XY: 16710 AN XY: 94550

Gnomad4 AFR exome AF: 0.395

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.146

Gnomad4 EAS exome AF: 0.0912

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.169

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.230 AC: 35062 AN: 152180 Hom.: 4911 Cov.: 32 AF XY: 0.229 AC XY: 17027 AN XY: 74420

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.0885

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.203

Alfa AF: 0.208 Hom.: 637

Bravo AF: 0.239

Asia WGS AF: 0.202 AC: 699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.1
Dann	Benign	0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7948948; hg19: chr11-122928175;