rs2236659

Positions:

• chr11-123062473-A-G

Variant summary

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

The ENST00000525624.5(HSPA8):​c.-6+277T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,232 control chromosomes in the GnomAD database, including 1,475 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 0.11 (1475 hom., cov: 33)
  • Exomes 𝑓: 0.039 (0 hom.)
• Consequence: HSPA8 ENST00000525624.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.123062473A>G		intergenic_region
HSPA8	XM_011542798.2	c.-132T>C		upstream_gene_variant			XP_011541100.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA8	ENST00000525624.5	c.-6+277T>C		intron_variant		5		ENSP00000435154.1
HSPA8	ENST00000532780.5	n.197T>C		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16375 AN: 152038 Hom.: 1462 Cov.: 33

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0786

Gnomad ASJ AF: 0.0303

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0322

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0427

Gnomad OTH AF: 0.0821

GnomAD4 exome AF: 0.0395 AC: 3 AN: 76 Hom.: 0 Cov.: 0 AF XY: 0.0313 AC XY: 2 AN XY: 64

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0385

GnomAD4 genome AF: 0.108 AC: 16427 AN: 152156 Hom.: 1475 Cov.: 33 AF XY: 0.109 AC XY: 8120 AN XY: 74396

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.0787

Gnomad4 ASJ AF: 0.0303

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.0322

Gnomad4 NFE AF: 0.0427

Gnomad4 OTH AF: 0.0812

Alfa AF: 0.0791 Hom.: 108

Bravo AF: 0.115

Asia WGS AF: 0.165 AC: 574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2236659; hg19: chr11-122933181;