Variant rs562047 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005345.6(HSPA1A):c.330G>C(p.Glu110Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.15 ( 831 hom., cov: 6)

Exomes 𝑓: 0.12 ( 5806 hom. )

Failed GnomAD Quality Control

Consequence

HSPA1A
NM_005345.6 missense

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: 3.54

Variant links:

Genes affected

HSPA1A (HGNC:5232): (heat shock protein family A (Hsp70) member 1A) This intronless gene encodes a 70kDa heat shock protein which is a member of the heat shock protein 70 family. In conjuction 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. It is also involved in the ubiquitin-proteasome pathway through interaction with the AU-rich element RNA-binding protein 1. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which encode similar proteins. [provided by RefSeq, Jul 2008]

HSPA1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033769608).

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA1A	NM_005345.6 linkuse as main transcript	c.330G>C	p.Glu110Asp	missense_variant	1/1	ENST00000375651.7	NP_005336.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA1A	ENST00000375651.7 linkuse as main transcript	c.330G>C	p.Glu110Asp	missense_variant	1/1		NM_005345.6	ENSP00000364802	P1	P0DMV8-1
HSPA1A	ENST00000608703.1 linkuse as main transcript	c.76-241G>C		intron_variant		2		ENSP00000477378

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

5461

AN:

35902

Hom.:

828

Cov.:

FAILED QC

Gnomad AFR

AF:

0.379

Gnomad AMI

AF:

0.0309

Gnomad AMR

AF:

0.164

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.0745

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.0522

Gnomad MID

AF:

0.229

Gnomad NFE

AF:

0.0856

Gnomad OTH

AF:

0.207

GnomAD3 exomes

AF:

0.158

AC:

10593

AN:

67108

Hom.:

1140

AF XY:

0.153

AC XY:

5272

AN XY:

34434

show subpopulations

Gnomad AFR exome

AF:

0.445

Gnomad AMR exome

AF:

0.157

Gnomad ASJ exome

AF:

0.236

Gnomad EAS exome

AF:

0.115

Gnomad SAS exome

AF:

0.134

Gnomad FIN exome

AF:

0.0756

Gnomad NFE exome

AF:

0.114

Gnomad OTH exome

AF:

0.161

GnomAD4 exome

AF:

0.124

AC:

71861

AN:

581384

Hom.:

5806

Cov.:

AF XY:

0.123

AC XY:

37004

AN XY:

301390

show subpopulations

Gnomad4 AFR exome

AF:

0.435

Gnomad4 AMR exome

AF:

0.160

Gnomad4 ASJ exome

AF:

0.238

Gnomad4 EAS exome

AF:

0.0865

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.0762

Gnomad4 NFE exome

AF:

0.107

Gnomad4 OTH exome

AF:

0.145

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.152

AC:

5467

AN:

35910

Hom.:

831

Cov.:

AF XY:

0.155

AC XY:

2279

AN XY:

14728

show subpopulations

Gnomad4 AFR

AF:

0.378

Gnomad4 AMR

AF:

0.163

Gnomad4 ASJ

AF:

0.187

Gnomad4 EAS

AF:

0.0746

Gnomad4 SAS

AF:

0.117

Gnomad4 FIN

AF:

0.0522

Gnomad4 NFE

AF:

0.0856

Gnomad4 OTH

AF:

0.204

Alfa

AF:

0.162

Hom.:

407

ExAC

AF:

0.0481

AC:

1492

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Chronic obstructive pulmonary disease

Other:1

association, no assertion criteria provided

case-control

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Aug 04, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

Eigen

Benign

0.0041

Eigen_PC

Benign

0.069

FATHMM_MKL

Uncertain

0.96

MetaRNN

Benign

0.0034

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.0000035

P;P;P

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-2.2

REVEL

Benign

0.11

Sift

Benign

0.042

Sift4G

Uncertain

0.029

Vest4

0.059

MutPred

0.24

Loss of phosphorylation at Y107 (P = 0.0735);

ClinPred

0.013

GERP RS

3.5

Varity_R

0.56

gMVP

0.18

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