13-31149028-A-G

Position:

• chr13-31149028-A-G

Variant summary

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

The NM_006644.4(HSPH1):​c.1138-548T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 151,972 control chromosomes in the GnomAD database, including 33,485 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 0.66 (33485 hom., cov: 32)
• Consequence: HSPH1 NM_006644.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08

Genes affected

HSPH1 (HGNC:16969): (heat shock protein family H (Hsp110) member 1) This gene encodes a member of the heat shock protein 70 family of proteins. The encoded protein functions as a nucleotide exchange factor for the molecular chaperone heat shock cognate 71 kDa protein (Hsc70). In addition, this protein plays a distinct but related role as a holdase that inhibits the aggregation of misfolded proteins, including the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Elevated expression of this protein has been observed in numerous human cancers. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPH1	NM_006644.4	c.1138-548T>C		intron_variant		ENST00000320027.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPH1	ENST00000320027.10	c.1138-548T>C		intron_variant		1	NM_006644.4	P1

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100449 AN: 151854 Hom.: 33477 Cov.: 32

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.717

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.649

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.661 AC: 100493 AN: 151972 Hom.: 33485 Cov.: 32 AF XY: 0.656 AC XY: 48722 AN XY: 74272

Gnomad4 AFR AF: 0.633

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.636

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.644

Alfa AF: 0.685 Hom.: 4460

Bravo AF: 0.665

Asia WGS AF: 0.494 AC: 1718 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.60

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: rs9315114; hg19: chr13-31723165;