rs1061581

Positions:

• chr6-31816809-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_005345.6(HSPA1A):​c.1053G>A​(p.Gln351=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HSPA1A NM_005345.6 synonymous
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.527

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=0.527 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA1A	NM_005345.6	c.1053G>A	p.Gln351=	synonymous_variant	1/1	ENST00000375651.7	NP_005336.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA1A	ENST00000375651.7	c.1053G>A	p.Gln351=	synonymous_variant	1/1		NM_005345.6	ENSP00000364802	P1
HSPA1A	ENST00000608703.1	c.558G>A	p.Gln186=	synonymous_variant	2/2	2		ENSP00000477378

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0150 AC: 1431 AN: 95294 Hom.: 0 Cov.: 0 AF XY: 0.0151 AC XY: 766 AN XY: 50784

Gnomad4 AFR exome AF: 0.00268

Gnomad4 AMR exome AF: 0.00746

Gnomad4 ASJ exome AF: 0.0269

Gnomad4 EAS exome AF: 0.0142

Gnomad4 SAS exome AF: 0.0206

Gnomad4 FIN exome AF: 0.00964

Gnomad4 NFE exome AF: 0.0149

Gnomad4 OTH exome AF: 0.0136

GnomAD4 genome Cov.: 0

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	9.0
DANN	Benign	0.93

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

Other links and lift over

dbSNP: rs1061581; hg19: chr6-31784586; COSMIC: COSV65148701; COSMIC: COSV65148701;