rs11218941

Positions:

• chr11-123061701-A-G
• chr11-123061701-A-T

Variant summary

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

The NM_006597.6(HSPA8):​c.-6+363T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 280,018 control chromosomes in the GnomAD database, including 10,776 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 0.28 (7154 hom., cov: 32)
  • Exomes 𝑓: 0.22 (3622 hom.)
• Consequence: HSPA8 NM_006597.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA8	NM_006597.6	c.-6+363T>C		intron_variant		ENST00000534624.6	NP_006588.1
HSPA8	NM_153201.4	c.-6+363T>C		intron_variant			NP_694881.1
HSPA8	XM_011542798.2	c.-5-372T>C		intron_variant			XP_011541100.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA8	ENST00000534624.6	c.-6+363T>C		intron_variant		1	NM_006597.6	ENSP00000432083	P1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42407 AN: 151908 Hom.: 7133 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.217 AC: 27793 AN: 127992 Hom.: 3622 Cov.: 0 AF XY: 0.223 AC XY: 15481 AN XY: 69546

Gnomad4 AFR exome AF: 0.468

Gnomad4 AMR exome AF: 0.217

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.441

Gnomad4 SAS exome AF: 0.285

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.174

Gnomad4 OTH exome AF: 0.210

GnomAD4 genome AF: 0.279 AC: 42486 AN: 152026 Hom.: 7154 Cov.: 32 AF XY: 0.280 AC XY: 20814 AN XY: 74344

Gnomad4 AFR AF: 0.463

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.240

Alfa AF: 0.201 Hom.: 4487

Bravo AF: 0.292

Asia WGS AF: 0.353 AC: 1226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.91
DANN	Benign	0.47

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: rs11218941; hg19: chr11-122932409;