rs4935825

Positions:

• chr11-123061657-A-C
• chr11-123061657-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.-5-328T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 384,710 control chromosomes in the GnomAD database, including 21,784 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 (7387 hom., cov: 32)
  • Exomes 𝑓: 0.33 (14397 hom.)
• Consequence: HSPA8 NM_006597.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.29

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 (NFE) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA8	NM_006597.6	c.-5-328T>G		intron_variant		ENST00000534624.6
HSPA8	NM_153201.4	c.-5-328T>G		intron_variant
HSPA8	XM_011542798.2	c.-5-328T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA8	ENST00000534624.6	c.-5-328T>G		intron_variant		1	NM_006597.6	P1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42350 AN: 151906 Hom.: 7386 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.00559

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.314

GnomAD4 exome AF: 0.332 AC: 77298 AN: 232686 Hom.: 14397 Cov.: 0 AF XY: 0.329 AC XY: 41246 AN XY: 125398

Gnomad4 AFR exome AF: 0.0862

Gnomad4 AMR exome AF: 0.224

Gnomad4 ASJ exome AF: 0.398

Gnomad4 EAS exome AF: 0.00124

Gnomad4 SAS exome AF: 0.272

Gnomad4 FIN exome AF: 0.368

Gnomad4 NFE exome AF: 0.391

Gnomad4 OTH exome AF: 0.331

GnomAD4 genome AF: 0.279 AC: 42352 AN: 152024 Hom.: 7387 Cov.: 32 AF XY: 0.271 AC XY: 20140 AN XY: 74302

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.00560

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.315

Alfa AF: 0.266 Hom.: 996

Bravo AF: 0.263

Asia WGS AF: 0.141 AC: 493 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	0.018
DANN	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs4935825; hg19: chr11-122932365;