rs562047
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_005345.6(HSPA1A):āc.330G>Cā(p.Glu110Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).
Frequency
Genomes: š 0.15 ( 831 hom., cov: 6)
Exomes š: 0.12 ( 5806 hom. )
Failed GnomAD Quality Control
Consequence
HSPA1A
NM_005345.6 missense
NM_005345.6 missense
Scores
4
11
Clinical Significance
Conservation
PhyloP100: 3.54
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0033769608).
BA1
?
GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSPA1A | NM_005345.6 | c.330G>C | p.Glu110Asp | missense_variant | 1/1 | ENST00000375651.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSPA1A | ENST00000375651.7 | c.330G>C | p.Glu110Asp | missense_variant | 1/1 | NM_005345.6 | P1 | ||
HSPA1A | ENST00000608703.1 | c.76-241G>C | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 5461AN: 35902Hom.: 828 Cov.: 6 FAILED QC
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GnomAD3 exomes AF: 0.158 AC: 10593AN: 67108Hom.: 1140 AF XY: 0.153 AC XY: 5272AN XY: 34434
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GnomAD4 exome AF: 0.124 AC: 71861AN: 581384Hom.: 5806 Cov.: 7 AF XY: 0.123 AC XY: 37004AN XY: 301390
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.152 AC: 5467AN: 35910Hom.: 831 Cov.: 6 AF XY: 0.155 AC XY: 2279AN XY: 14728
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Data not reliable, filtered out with message: AS_VQSR
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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:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
P;P;P
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
D
Sift4G
Uncertain
D
Vest4
MutPred
Loss of phosphorylation at Y107 (P = 0.0735);
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at