Genetic Variant HSPA1A:c.-27G>C (chr6-31815730-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

129 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HSPA1A	NM_005345.6 link	c.-27G>C		5_prime_UTR_variant	Exon 1 of 1	ENST00000375651.7	NP_005336.3	P0DMV8-1P0DMV9A8K5I0B3KTT5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA1A	ENST00000375651.7 link	c.-27G>C		5_prime_UTR_variant	Exon 1 of 1	6	NM_005345.6	ENSP00000364802.5		P0DMV8-1
HSPA1A	ENST00000608703.2 link	c.-27G>C		5_prime_UTR_variant	Exon 1 of 2	2		ENSP00000477378.1		V9GZ37

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

GnomAD2 exomes

AF:

0.389

AC:

97716

AN:

250976

AF XY:

0.386

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 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

African (AFR)

AF:

0.750

AC:

25097

AN:

33480

American (AMR)

AF:

0.304

AC:

13594

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.369

AC:

9650

AN:

26126

East Asian (EAS)

AF:

0.243

AC:

9647

AN:

39698

South Asian (SAS)

AF:

0.396

AC:

34136

AN:

86242

European-Finnish (FIN)

AF:

0.461

AC:

24507

AN:

53104

Middle Eastern (MID)

AF:

0.415

AC:

2395

AN:

5766

European-Non Finnish (NFE)

AF:

0.376

AC:

417955

AN:

1111956

Other (OTH)

AF:

0.406

AC:

24529

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

25261

50522

75782

101043

126304

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.481

AC:

73202

AN:

152140

Hom.:

19690

Cov.:

AF XY:

0.480

AC XY:

35671

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.736

AC:

30529

AN:

41504

American (AMR)

AF:

0.369

AC:

5647

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.365

AC:

1266

AN:

3472

East Asian (EAS)

AF:

0.294

AC:

1520

AN:

5162

South Asian (SAS)

AF:

0.421

AC:

2032

AN:

4826

European-Finnish (FIN)

AF:

0.481

AC:

5089

AN:

10576

Middle Eastern (MID)

AF:

0.459

AC:

135

AN:

294

European-Non Finnish (NFE)

AF:

0.378

AC:

25722

AN:

67990

Other (OTH)

AF:

0.489

AC:

1033

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1798

3596

5393

7191

8989

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Aug 04, 2019

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance:association

Review Status:no assertion criteria provided

Collection Method:case-control

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.61

(source)

DANN

Benign

0.51

PhyloP100

-1.3

PromoterAI

0.0096

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=296/4

polymorphism (auto)

(source)

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

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6-31815730-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over