rs1064585

Positions:

• chr11-123058699-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006597.6(HSPA8):​c.1455A>C​(p.Ile485Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,612,996 control chromosomes in the GnomAD database, including 29,050 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 (4957 hom., cov: 32)
  • Exomes 𝑓: 0.17 (24093 hom.)
• Consequence: HSPA8 NM_006597.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.582

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]

HSPA8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=0.582 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA8	NM_006597.6	c.1455A>C	p.Ile485Ile	synonymous_variant	7/9	ENST00000534624.6	NP_006588.1
HSPA8	XM_011542798.2	c.1455A>C	p.Ile485Ile	synonymous_variant	7/9		XP_011541100.1
HSPA8	NM_153201.4	c.1387+68A>C		intron_variant			NP_694881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA8	ENST00000534624.6	c.1455A>C	p.Ile485Ile	synonymous_variant	7/9	1	NM_006597.6	ENSP00000432083.1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35140 AN: 151964 Hom.: 4940 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0874

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.209

GnomAD3 exomes AF: 0.185 AC: 46499 AN: 251378 Hom.: 4937 AF XY: 0.184 AC XY: 25048 AN XY: 135880

Gnomad AFR exome AF: 0.404

Gnomad AMR exome AF: 0.176

Gnomad ASJ exome AF: 0.133

Gnomad EAS exome AF: 0.0900

Gnomad SAS exome AF: 0.256

Gnomad FIN exome AF: 0.152

Gnomad NFE exome AF: 0.165

Gnomad OTH exome AF: 0.160

GnomAD4 exome AF: 0.174 AC: 254735 AN: 1460914 Hom.: 24093 Cov.: 34 AF XY: 0.176 AC XY: 128161 AN XY: 726838

Gnomad4 AFR exome AF: 0.412

Gnomad4 AMR exome AF: 0.178

Gnomad4 ASJ exome AF: 0.138

Gnomad4 EAS exome AF: 0.0909

Gnomad4 SAS exome AF: 0.253

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.165

Gnomad4 OTH exome AF: 0.184

GnomAD4 genome AF: 0.231 AC: 35206 AN: 152082 Hom.: 4957 Cov.: 32 AF XY: 0.230 AC XY: 17103 AN XY: 74354

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.0878

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.205

Alfa AF: 0.195 Hom.: 1526

Bravo AF: 0.241

Asia WGS AF: 0.195 AC: 675 AN: 3478

EpiCase AF: 0.169

EpiControl AF: 0.167

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.3
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1064585; hg19: chr11-122929407; COSMIC: COSV57083583; COSMIC: COSV57083583;