Variant chr6-31815730-G-C 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.-27G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 1,613,618 control chromosomes in the GnomAD database, including 131,593 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.48 ( 19690 hom., cov: 32)

Exomes 𝑓: 0.38 ( 111903 hom. )

Consequence

HSPA1A
NM_005345.6 5_prime_UTR

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: -1.28

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 (BayesDel_noAF=-0.53).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA1A	NM_005345.6 linkuse as main transcript	c.-27G>C		5_prime_UTR_variant	1/1	ENST00000375651.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA1A	ENST00000375651.7 linkuse as main transcript	c.-27G>C		5_prime_UTR_variant	1/1		NM_005345.6	P1	P0DMV8-1
HSPA1A	ENST00000608703.1 linkuse as main transcript	c.-27G>C		5_prime_UTR_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.481

AC:

73138

AN:

152022

Hom.:

19663

Cov.:

show subpopulations

Gnomad AFR

AF:

0.736

Gnomad AMI

AF:

0.251

Gnomad AMR

AF:

0.370

Gnomad ASJ

AF:

0.365

Gnomad EAS

AF:

0.294

Gnomad SAS

AF:

0.422

Gnomad FIN

AF:

0.481

Gnomad MID

AF:

0.472

Gnomad NFE

AF:

0.378

Gnomad OTH

AF:

0.488

GnomAD3 exomes

AF:

0.389

AC:

97716

AN:

250976

Hom.:

20634

AF XY:

0.386

AC XY:

52393

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.745

Gnomad AMR exome

AF:

0.289

Gnomad ASJ exome

AF:

0.365

Gnomad EAS exome

AF:

0.307

Gnomad SAS exome

AF:

0.393

Gnomad FIN exome

AF:

0.461

Gnomad NFE exome

AF:

0.370

Gnomad OTH exome

AF:

0.396

GnomAD4 exome

AF:

0.384

AC:

561510

AN:

1461478

Hom.:

111903

Cov.:

AF XY:

0.383

AC XY:

278473

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.750

Gnomad4 AMR exome

AF:

0.304

Gnomad4 ASJ exome

AF:

0.369

Gnomad4 EAS exome

AF:

0.243

Gnomad4 SAS exome

AF:

0.396

Gnomad4 FIN exome

AF:

0.461

Gnomad4 NFE exome

AF:

0.376

Gnomad4 OTH exome

AF:

0.406

GnomAD4 genome

AF:

0.481

AC:

73202

AN:

152140

Hom.:

19690

Cov.:

AF XY:

0.480

AC XY:

35671

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.736

Gnomad4 AMR

AF:

0.369

Gnomad4 ASJ

AF:

0.365

Gnomad4 EAS

AF:

0.294

Gnomad4 SAS

AF:

0.421

Gnomad4 FIN

AF:

0.481

Gnomad4 NFE

AF:

0.378

Gnomad4 OTH

AF:

0.489

Alfa

AF:

0.304

Hom.:

1183

Bravo

AF:

0.484

Asia WGS

AF:

0.423

AC:

1470

AN:

3478

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_noAF

Benign

-0.53

CADD

Benign

0.61

DANN

Benign

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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