rs2276075

Positions:

• chr11-123062094-G-A
• chr11-123062094-G-T

Variant summary

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

The NM_006597.6(HSPA8):​c.-36C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0642 in 152,844 control chromosomes in the GnomAD database, including 379 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 0.064 (376 hom., cov: 33)
  • Exomes 𝑓: 0.055 (3 hom.)
• Consequence: HSPA8 NM_006597.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.62

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA8	NM_006597.6	c.-36C>T		5_prime_UTR_variant	1/9	ENST00000534624.6	NP_006588.1
HSPA8	NM_153201.4	c.-36C>T		5_prime_UTR_variant	1/8		NP_694881.1
HSPA8	XM_011542798.2	c.-6+253C>T		intron_variant			XP_011541100.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA8	ENST00000534624.6	c.-36C>T		5_prime_UTR_variant	1/9	1	NM_006597.6	ENSP00000432083	P1

Frequencies

GnomAD3 genomes AF: 0.0642 AC: 9763 AN: 152004 Hom.: 376 Cov.: 33

Gnomad AFR AF: 0.0549

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.0522

Gnomad FIN AF: 0.0619

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0513

Gnomad OTH AF: 0.0638

GnomAD4 exome AF: 0.0554 AC: 40 AN: 722 Hom.: 3 Cov.: 0 AF XY: 0.0566 AC XY: 31 AN XY: 548

Gnomad4 AFR exome AF: 0.0556

Gnomad4 AMR exome AF: 0.167

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.0417

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0500

Gnomad4 OTH exome AF: 0.0455

GnomAD4 genome AF: 0.0643 AC: 9775 AN: 152122 Hom.: 376 Cov.: 33 AF XY: 0.0685 AC XY: 5094 AN XY: 74344

Gnomad4 AFR AF: 0.0549

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.0778

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.0529

Gnomad4 FIN AF: 0.0619

Gnomad4 NFE AF: 0.0513

Gnomad4 OTH AF: 0.0651

Alfa AF: 0.0598 Hom.: 302

Bravo AF: 0.0707

Asia WGS AF: 0.0940 AC: 326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.48
DANN	Benign	0.72
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2276075; hg19: chr11-122932802;