Variant 6-31815599-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1321 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA1A	NM_005345.6 linkuse as main transcript	c.-158C>A		5_prime_UTR_variant	1/1	ENST00000375651.7	NP_005336.3	P0DMV8-1P0DMV9A8K5I0B3KTT5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA1A	ENST00000375651.7 linkuse as main transcript	c.-158C>A		5_prime_UTR_variant	1/1	6	NM_005345.6	ENSP00000364802.5		P0DMV8-1
HSPA1A	ENST00000608703.1 linkuse as main transcript	c.-158C>A		5_prime_UTR_variant	1/2	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

Gnomad4 AFR exome

AF:

0.00318

Gnomad4 AMR exome

AF:

0.00479

Gnomad4 ASJ exome

AF:

0.00820

Gnomad4 EAS exome

AF:

0.00660

Gnomad4 SAS exome

AF:

0.0383

Gnomad4 FIN exome

AF:

0.00959

Gnomad4 NFE exome

AF:

0.00944

Gnomad4 OTH exome

AF:

0.0123

GnomAD4 genome

AF:

0.00867

AC:

1321

AN:

152346

Hom.:

Cov.:

AF XY:

0.00932

AC XY:

694

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00368

Gnomad4 AMR

AF:

0.00810

Gnomad4 ASJ

AF:

0.00836

Gnomad4 EAS

AF:

0.0102

Gnomad4 SAS

AF:

0.0348

Gnomad4 FIN

AF:

0.00885

Gnomad4 NFE

AF:

0.0100

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.00290

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

DANN

Benign

0.56

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over