rs2227955
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_005527.4(HSPA1L):āc.1673A>Cā(p.Glu558Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0296 in 1,558,830 control chromosomes in the GnomAD database, including 927 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.041 ( 187 hom., cov: 32)
Exomes š: 0.028 ( 740 hom. )
Consequence
HSPA1L
NM_005527.4 missense
NM_005527.4 missense
Scores
1
4
12
Clinical Significance
Conservation
PhyloP100: 6.27
Genes affected
HSPA1L (HGNC:5234): (heat shock protein family A (Hsp70) member 1 like) This gene encodes a 70kDa heat shock protein. In conjunction 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. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which also encode isoforms of the 70kDa heat shock protein. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0021847188).
BP6
?
Variant 6-31810300-T-G is Benign according to our data. Variant chr6-31810300-T-G is described in ClinVar as [Benign]. Clinvar id is 372131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0805 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSPA1L | NM_005527.4 | c.1673A>C | p.Glu558Ala | missense_variant | 2/2 | ENST00000375654.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSPA1L | ENST00000375654.5 | c.1673A>C | p.Glu558Ala | missense_variant | 2/2 | 1 | NM_005527.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0415 AC: 6315AN: 152140Hom.: 187 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0318 AC: 6531AN: 205372Hom.: 166 AF XY: 0.0313 AC XY: 3448AN XY: 110132
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GnomAD4 exome AF: 0.0284 AC: 39887AN: 1406572Hom.: 740 Cov.: 36 AF XY: 0.0289 AC XY: 20117AN XY: 695544
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GnomAD4 genome ? AF: 0.0415 AC: 6316AN: 152258Hom.: 187 Cov.: 32 AF XY: 0.0412 AC XY: 3070AN XY: 74446
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ALSPAC
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112
ESP6500AA
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356
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ExAC
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4010
Asia WGS
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125
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ClinVar
Significance: Benign
Submissions summary: Benign:2Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 10, 2019 | This variant is associated with the following publications: (PMID: 28126021) - |
HSPA1L-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 23, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Inflammatory bowel disease 1 Other:1
association, no assertion criteria provided | research | Human Development and Health, University of Southampton | Aug 06, 2016 | HSPA1L loss of function - Our results indicate that de novo and rare mutations in HSPA1L are associated with IBD and provide insights into the pathogenesis of IBD - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
B
Vest4
MPC
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