Variant 6-31810300-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005527.4(HSPA1L):c.1673A>C(p.Glu558Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0296 in 1,558,830 control chromosomes in the GnomAD database, including 927 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.041 ( 187 hom., cov: 32)

Exomes 𝑓: 0.028 ( 740 hom. )

Consequence

HSPA1L
NM_005527.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2O:1

Conservation

PhyloP100: 6.27

Variant links:

Genes affected

HSPA1L (HGNC:5234): (heat shock protein family A (Hsp70) member 1 like) This gene encodes a 70kDa heat shock protein. In conjunction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which also encode isoforms of the 70kDa heat shock protein. [provided by RefSeq, Jul 2008]

HSPA1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021847188).

BP6

Variant 6-31810300-T-G is Benign according to our data. Variant chr6-31810300-T-G is described in ClinVar as [Benign]. Clinvar id is 372131.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA1L	NM_005527.4 linkuse as main transcript	c.1673A>C	p.Glu558Ala	missense_variant	2/2	ENST00000375654.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA1L	ENST00000375654.5 linkuse as main transcript	c.1673A>C	p.Glu558Ala	missense_variant	2/2	1	NM_005527.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0415

AC:

6315

AN:

152140

Hom.:

187

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0830

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0305

Gnomad ASJ

AF:

0.0113

Gnomad EAS

AF:

0.0137

Gnomad SAS

AF:

0.0397

Gnomad FIN

AF:

0.0156

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0271

Gnomad OTH

AF:

0.0406

GnomAD3 exomes

AF:

0.0318

AC:

6531

AN:

205372

Hom.:

166

AF XY:

0.0313

AC XY:

3448

AN XY:

110132

show subpopulations

Gnomad AFR exome

AF:

0.0847

Gnomad AMR exome

AF:

0.0326

Gnomad ASJ exome

AF:

0.0123

Gnomad EAS exome

AF:

0.00951

Gnomad SAS exome

AF:

0.0443

Gnomad FIN exome

AF:

0.0186

Gnomad NFE exome

AF:

0.0283

Gnomad OTH exome

AF:

0.0264

GnomAD4 exome

AF:

0.0284

AC:

39887

AN:

1406572

Hom.:

740

Cov.:

AF XY:

0.0289

AC XY:

20117

AN XY:

695544

show subpopulations

Gnomad4 AFR exome

AF:

0.0858

Gnomad4 AMR exome

AF:

0.0318

Gnomad4 ASJ exome

AF:

0.0114

Gnomad4 EAS exome

AF:

0.0140

Gnomad4 SAS exome

AF:

0.0436

Gnomad4 FIN exome

AF:

0.0189

Gnomad4 NFE exome

AF:

0.0267

Gnomad4 OTH exome

AF:

0.0312

GnomAD4 genome

AF:

0.0415

AC:

6316

AN:

152258

Hom.:

187

Cov.:

AF XY:

0.0412

AC XY:

3070

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0829

Gnomad4 AMR

AF:

0.0304

Gnomad4 ASJ

AF:

0.0113

Gnomad4 EAS

AF:

0.0137

Gnomad4 SAS

AF:

0.0400

Gnomad4 FIN

AF:

0.0156

Gnomad4 NFE

AF:

0.0271

Gnomad4 OTH

AF:

0.0402

Alfa

AF:

0.0295

Hom.:

155

Bravo

AF:

0.0436

TwinsUK

AF:

0.0280

AC:

104

ALSPAC

AF:

0.0291

AC:

112

ESP6500AA

AF:

0.0808

AC:

356

ESP6500EA

AF:

0.0264

AC:

227

ExAC

AF:

0.0330

AC:

4010

Asia WGS

AF:

0.0350

AC:

125

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

This variant is associated with the following publications: (PMID: 28126021) -

HSPA1L-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 23, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Inflammatory bowel disease 1

Other:1

association, no assertion criteria provided

research

Human Development and Health, University of Southampton

Aug 06, 2016

HSPA1L loss of function - Our results indicate that de novo and rare mutations in HSPA1L are associated with IBD and provide insights into the pathogenesis of IBD -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.97

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.94

MutationTaster

Benign

0.97

D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.1

REVEL

Benign

0.054

Sift

Uncertain

0.0080

Sift4G

Benign

0.21

Polyphen

0.30

Vest4

0.25

MPC

0.40

ClinPred

0.040

GERP RS

4.8

Varity_R

0.11

gMVP

0.31

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