11-123058167-C-T

Position:

• chr11-123058167-C-T

Variant summary

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

The NM_006597.6(HSPA8):​c.1755+85G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 903,328 control chromosomes in the GnomAD database, including 41,730 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 0.34 (9941 hom., cov: 27)
  • Exomes 𝑓: 0.27 (31789 hom.)
• Consequence: HSPA8 NM_006597.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

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]

HSPA8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA8	NM_006597.6	c.1755+85G>A		intron_variant		ENST00000534624.6	NP_006588.1
HSPA8	NM_153201.4	c.1388-339G>A		intron_variant			NP_694881.1
HSPA8	XM_011542798.2	c.1755+85G>A		intron_variant			XP_011541100.1
SNORD14E	NR_003125.2	n.-11G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA8	ENST00000534624.6	c.1755+85G>A		intron_variant		1	NM_006597.6	ENSP00000432083.1

Frequencies

GnomAD3 genomes AF: 0.342 AC: 50907 AN: 149040 Hom.: 9910 Cov.: 27

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.306

GnomAD4 exome AF: 0.272 AC: 205054 AN: 754178 Hom.: 31789 Cov.: 10 AF XY: 0.273 AC XY: 107839 AN XY: 395254

Gnomad4 AFR exome AF: 0.521

Gnomad4 AMR exome AF: 0.415

Gnomad4 ASJ exome AF: 0.234

Gnomad4 EAS exome AF: 0.576

Gnomad4 SAS exome AF: 0.350

Gnomad4 FIN exome AF: 0.229

Gnomad4 NFE exome AF: 0.227

Gnomad4 OTH exome AF: 0.283

GnomAD4 genome AF: 0.342 AC: 50993 AN: 149150 Hom.: 9941 Cov.: 27 AF XY: 0.347 AC XY: 25213 AN XY: 72584

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.306

Alfa AF: 0.281 Hom.: 2182

Bravo AF: 0.362

Asia WGS AF: 0.446 AC: 1547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.19
DANN	Benign	0.77

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: rs4936770; hg19: chr11-122928875; COSMIC: COSV57083402; COSMIC: COSV57083402;