11-123061470-C-A

Position:

• chr11-123061470-C-A

Variant summary

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

The NM_006597.6(HSPA8):​c.-5-141G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0174 in 678,938 control chromosomes in the GnomAD database, including 753 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 0.024 (179 hom., cov: 32)
  • Exomes 𝑓: 0.016 (574 hom.)
• Consequence: HSPA8 NM_006597.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA8	NM_006597.6	c.-5-141G>T		intron_variant		ENST00000534624.6
HSPA8	NM_153201.4	c.-5-141G>T		intron_variant
HSPA8	XM_011542798.2	c.-5-141G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA8	ENST00000534624.6	c.-5-141G>T		intron_variant		1	NM_006597.6	P1

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3628 AN: 152148 Hom.: 179 Cov.: 32

Gnomad AFR AF: 0.0530

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.00870

Gnomad FIN AF: 0.00622

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00106

Gnomad OTH AF: 0.0191

GnomAD4 exome AF: 0.0156 AC: 8208 AN: 526672 Hom.: 574 Cov.: 6 AF XY: 0.0144 AC XY: 4031 AN XY: 279108

Gnomad4 AFR exome AF: 0.0486

Gnomad4 AMR exome AF: 0.00589

Gnomad4 ASJ exome AF: 0.0133

Gnomad4 EAS exome AF: 0.177

Gnomad4 SAS exome AF: 0.00482

Gnomad4 FIN exome AF: 0.00691

Gnomad4 NFE exome AF: 0.00131

Gnomad4 OTH exome AF: 0.0221

GnomAD4 genome AF: 0.0239 AC: 3638 AN: 152266 Hom.: 179 Cov.: 32 AF XY: 0.0244 AC XY: 1815 AN XY: 74456

Gnomad4 AFR AF: 0.0529

Gnomad4 AMR AF: 0.0119

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.00870

Gnomad4 FIN AF: 0.00622

Gnomad4 NFE AF: 0.00106

Gnomad4 OTH AF: 0.0223

Alfa AF: 0.00635 Hom.: 114

Bravo AF: 0.0263

Asia WGS AF: 0.0840 AC: 291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.28

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: rs11823704; hg19: chr11-122932178;