Variant 13-31148483-TAAAA-TAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_006644.4(HSPH1):c.1138-4del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.42 ( 9623 hom., cov: 0)

Exomes 𝑓: 0.42 ( 3817 hom. )

Failed GnomAD Quality Control

Consequence

HSPH1
NM_006644.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.36

Variant links:

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]

HSPH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 13-31148483-TA-T is Benign according to our data. Variant chr13-31148483-TA-T is described in ClinVar as [Benign]. Clinvar id is 402951.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-31148483-TA-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPH1	NM_006644.4 linkuse as main transcript	c.1138-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000320027.10	NP_006635.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPH1	ENST00000320027.10 linkuse as main transcript	c.1138-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006644.4	ENSP00000318687	P1	Q92598-1

Frequencies

GnomAD3 genomes

AF:

0.416

AC:

49446

AN:

118872

Hom.:

9629

Cov.:

show subpopulations

Gnomad AFR

AF:

0.314

Gnomad AMI

AF:

0.683

Gnomad AMR

AF:

0.388

Gnomad ASJ

AF:

0.385

Gnomad EAS

AF:

0.0237

Gnomad SAS

AF:

0.234

Gnomad FIN

AF:

0.467

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.500

Gnomad OTH

AF:

0.402

GnomAD3 exomes

AF:

0.463

AC:

50425

AN:

108980

Hom.:

AF XY:

0.461

AC XY:

27720

AN XY:

60134

show subpopulations

Gnomad AFR exome

AF:

0.464

Gnomad AMR exome

AF:

0.459

Gnomad ASJ exome

AF:

0.443

Gnomad EAS exome

AF:

0.448

Gnomad SAS exome

AF:

0.440

Gnomad FIN exome

AF:

0.468

Gnomad NFE exome

AF:

0.468

Gnomad OTH exome

AF:

0.470

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.423

AC:

361769

AN:

855930

Hom.:

3817

Cov.:

AF XY:

0.423

AC XY:

181729

AN XY:

429722

show subpopulations

Gnomad4 AFR exome

AF:

0.399

Gnomad4 AMR exome

AF:

0.427

Gnomad4 ASJ exome

AF:

0.421

Gnomad4 EAS exome

AF:

0.410

Gnomad4 SAS exome

AF:

0.376

Gnomad4 FIN exome

AF:

0.433

Gnomad4 NFE exome

AF:

0.426

Gnomad4 OTH exome

AF:

0.420

GnomAD4 genome

AF:

0.416

AC:

49428

AN:

118860

Hom.:

9623

Cov.:

AF XY:

0.411

AC XY:

23075

AN XY:

56156

show subpopulations

Gnomad4 AFR

AF:

0.314

Gnomad4 AMR

AF:

0.387

Gnomad4 ASJ

AF:

0.385

Gnomad4 EAS

AF:

0.0241

Gnomad4 SAS

AF:

0.233

Gnomad4 FIN

AF:

0.467

Gnomad4 NFE

AF:

0.499

Gnomad4 OTH

AF:

0.401

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over