rs41302367

chr11-123061474-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.-5-145C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0354 in 661,116 control chromosomes in the GnomAD database, including 2,179 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 0.074 (1213 hom., cov: 32)
  • Exomes 𝑓: 0.024 (966 hom.)
• Consequence: HSPA8 NM_006597.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA8	NM_006597.6	c.-5-145C>T		intron_variant		ENST00000534624.6
HSPA8	NM_153201.4	c.-5-145C>T		intron_variant
HSPA8	XM_011542798.2	c.-5-145C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA8	ENST00000534624.6	c.-5-145C>T		intron_variant		1	NM_006597.6	P1

Frequencies

GnomAD3 genomes AF: 0.0735 AC: 11182 AN: 152096 Hom.: 1200 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0307

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.0193

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00288

Gnomad OTH AF: 0.0512

GnomAD4 exome AF: 0.0239 AC: 12164 AN: 508902 Hom.: 966 Cov.: 6 AF XY: 0.0279 AC XY: 7542 AN XY: 270068

Gnomad4 AFR exome AF: 0.235

Gnomad4 AMR exome AF: 0.0169

Gnomad4 ASJ exome AF: 0.0126

Gnomad4 EAS exome AF: 0.0104

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.0000324

Gnomad4 NFE exome AF: 0.00252

Gnomad4 OTH exome AF: 0.0314

GnomAD4 genome AF: 0.0738 AC: 11234 AN: 152214 Hom.: 1213 Cov.: 32 AF XY: 0.0742 AC XY: 5523 AN XY: 74426

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.0306

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.0193

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00287

Gnomad4 OTH AF: 0.0507

Alfa AF: 0.0443 Hom.: 86

Bravo AF: 0.0801

Asia WGS AF: 0.0980 AC: 339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	4.4
Dann	Benign	0.67

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: rs41302367; hg19: chr11-122932182;