rs2236658

chr11-123062424-T-C

Variant summary

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

The XM_011542798.2(HSPA8):c.-83A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,272 control chromosomes in the GnomAD database, including 2,566 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 0.14 (2566 hom., cov: 33)
  • Exomes 𝑓: 0.020 (0 hom.)
• Consequence: HSPA8 XM_011542798.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.660

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=-0.6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA8	XM_011542798.2	c.-83A>G		5_prime_UTR_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA8	ENST00000525624.5	c.-6+326A>G		intron_variant		5
HSPA8	ENST00000532780.5	n.246A>G		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20587 AN: 152002 Hom.: 2549 Cov.: 33

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0919

Gnomad ASJ AF: 0.0406

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.0385

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.0438

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.0197 AC: 3 AN: 152 Hom.: 0 Cov.: 0 AF XY: 0.0238 AC XY: 3 AN XY: 126

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0259

GnomAD4 genome AF: 0.136 AC: 20652 AN: 152120 Hom.: 2566 Cov.: 33 AF XY: 0.137 AC XY: 10218 AN XY: 74360

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.0921

Gnomad4 ASJ AF: 0.0406

Gnomad4 EAS AF: 0.389

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.0385

Gnomad4 NFE AF: 0.0438

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0941 Hom.: 187

Bravo AF: 0.146

Asia WGS AF: 0.259 AC: 897 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	17
Dann	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2236658; hg19: chr11-122933132;