rs9315114

Variant names:

• chr13-31149028-A-G
• rs9315114
• NM_006644.4:c.1138-548T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HSPH1	NM_006644.4	c.1138-548T>C		intron_variant	Intron 8 of 17	ENST00000320027.10	NP_006635.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPH1	ENST00000320027.10	c.1138-548T>C		intron_variant	Intron 8 of 17	1	NM_006644.4	ENSP00000318687.5
HSPH1	ENST00000602786.5	n.*666-548T>C		intron_variant	Intron 7 of 16	1		ENSP00000473512.1

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

African (AFR) AF: 0.633 AC: 26239 AN: 41470

American (AMR) AF: 0.657 AC: 10036 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2205 AN: 3468

East Asian (EAS) AF: 0.477 AC: 2466 AN: 5168

South Asian (SAS) AF: 0.558 AC: 2692 AN: 4822

European-Finnish (FIN) AF: 0.653 AC: 6882 AN: 10544

Middle Eastern (MID) AF: 0.726 AC: 212 AN: 292

European-Non Finnish (NFE) AF: 0.701 AC: 47640 AN: 67926

Other (OTH) AF: 0.644 AC: 1357 AN: 2106

Alfa AF: 0.684 Hom.: 4633

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
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9315114; hg19: chr13-31723165;