dbSNP rs33934112: HSPA1A:c.-158C>A (chr6-31815599-C-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2

The NM_005345.6(HSPA1A):c.-158C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,552,412 control chromosomes in the GnomAD database, including 164 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0087 ( 7 hom., cov: 32)

Exomes 𝑓: 0.011 ( 157 hom. )

Consequence

HSPA1A
NM_005345.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.100

Publications

4 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00867 (1321/152346) while in subpopulation SAS AF = 0.0348 (168/4828). AF 95% confidence interval is 0.0305. There are 7 homozygotes in GnomAd4. There are 694 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1321 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPA1A	NM_005345.6 link	c.-158C>A		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.-158C>A		5_prime_UTR_variant	Exon 1 of 1	6	NM_005345.6	ENSP00000364802.5		P0DMV8-1
HSPA1A	ENST00000608703.2 link	c.-158C>A		5_prime_UTR_variant	Exon 1 of 2	2		ENSP00000477378.1		V9GZ37

Frequencies

GnomAD3 genomes

AF:

0.00867

AC:

1320

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00369

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00811

Gnomad ASJ

AF:

0.00836

Gnomad EAS

AF:

0.0102

Gnomad SAS

AF:

0.0346

Gnomad FIN

AF:

0.00885

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00999

Gnomad OTH

AF:

0.00716

GnomAD4 exome

AF:

0.0109

AC:

15293

AN:

1400066

Hom.:

157

Cov.:

AF XY:

0.0120

AC XY:

8345

AN XY:

696830

show subpopulations

African (AFR)

AF:

0.00318

AC:

101

AN:

31790

American (AMR)

AF:

0.00479

AC:

191

AN:

39912

Ashkenazi Jewish (ASJ)

AF:

0.00820

AC:

209

AN:

25490

East Asian (EAS)

AF:

0.00660

AC:

252

AN:

38206

South Asian (SAS)

AF:

0.0383

AC:

3176

AN:

82916

European-Finnish (FIN)

AF:

0.00959

AC:

458

AN:

47758

Middle Eastern (MID)

AF:

0.0151

AC:

AN:

5682

European-Non Finnish (NFE)

AF:

0.00944

AC:

10106

AN:

1070056

Other (OTH)

AF:

0.0123

AC:

714

AN:

58256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

848

1695

2543

3390

4238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

378

756

1134

1512

1890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00867

AC:

1321

AN:

152346

Hom.:

Cov.:

AF XY:

0.00932

AC XY:

694

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.00368

AC:

153

AN:

41582

American (AMR)

AF:

0.00810

AC:

124

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00836

AC:

AN:

3470

East Asian (EAS)

AF:

0.0102

AC:

AN:

5188

South Asian (SAS)

AF:

0.0348

AC:

168

AN:

4828

European-Finnish (FIN)

AF:

0.00885

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0100

AC:

681

AN:

68034

Other (OTH)

AF:

0.00709

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

140

209

279

349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00611

Hom.:

Bravo

AF:

0.00770

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

4.2

(source)

DANN

Benign

0.56

PhyloP100

0.10

PromoterAI

0.066

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Mutation Taster

=300/0

polymorphism

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over