rs1136141

chr11-123062069-G-A

Variant summary

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

The NM_006597.6(HSPA8):c.-11C>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 0.143 in 152,516 control chromosomes in the GnomAD database, including 1,587 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 (1581 hom., cov: 33)
  • Exomes 𝑓: 0.13 (6 hom.)
• Consequence: HSPA8 NM_006597.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA8	NM_006597.6	c.-11C>T		5_prime_UTR_variant	1/9	ENST00000534624.6
HSPA8	NM_153201.4	c.-11C>T		5_prime_UTR_variant	1/8
HSPA8	XM_011542798.2	c.-6+278C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA8	ENST00000534624.6	c.-11C>T		5_prime_UTR_variant	1/9	1	NM_006597.6	P1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21712 AN: 151982 Hom.: 1581 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.0688

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.137

GnomAD4 exome AF: 0.128 AC: 53 AN: 414 Hom.: 6 Cov.: 0 AF XY: 0.114 AC XY: 33 AN XY: 290

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0600

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.0714

GnomAD4 genome AF: 0.143 AC: 21726 AN: 152102 Hom.: 1581 Cov.: 33 AF XY: 0.142 AC XY: 10550 AN XY: 74354

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.0691

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.134

Alfa AF: 0.139 Hom.: 2596

Bravo AF: 0.145

Asia WGS AF: 0.0960 AC: 332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	2.4
Dann	Benign	0.66
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1136141; hg19: chr11-122932777;