rs1050409
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002117.6(HLA-C):c.218C>T(p.Ala73Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,388,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 14)
Exomes 𝑓: 0.0000022 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
HLA-C
NM_002117.6 missense
NM_002117.6 missense
Scores
4
14
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.366
Publications
0 publications found
Genes affected
HLA-C (HGNC:4933): (major histocompatibility complex, class I, C) HLA-C belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domain, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. About 6000 HLA-C alleles have been described. The HLA system plays an important role in the occurrence and outcome of infectious diseases, including those caused by the malaria parasite, the human immunodeficiency virus (HIV), and the severe acute respiratory syndrome coronavirus (SARS-CoV). The structural spike and the nucleocapsid proteins of the novel coronavirus SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19), are reported to contain multiple Class I epitopes with predicted HLA restrictions. Individual HLA genetic variation may help explain different immune responses to a virus across a population.[provided by RefSeq, Aug 2020]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.105810404).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 97434Hom.: 0 Cov.: 14
GnomAD3 genomes
AF:
AC:
0
AN:
97434
Hom.:
Cov.:
14
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000216 AC: 3AN: 1388134Hom.: 0 Cov.: 39 AF XY: 0.00000289 AC XY: 2AN XY: 691976 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
3
AN:
1388134
Hom.:
Cov.:
39
AF XY:
AC XY:
2
AN XY:
691976
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
31282
American (AMR)
AF:
AC:
0
AN:
42794
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24964
East Asian (EAS)
AF:
AC:
1
AN:
37338
South Asian (SAS)
AF:
AC:
0
AN:
84008
European-Finnish (FIN)
AF:
AC:
0
AN:
49088
Middle Eastern (MID)
AF:
AC:
0
AN:
4784
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1057198
Other (OTH)
AF:
AC:
0
AN:
56678
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00 AC: 0AN: 97434Hom.: 0 Cov.: 14 AF XY: 0.00 AC XY: 0AN XY: 46874
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
AC:
0
AN:
97434
Hom.:
Cov.:
14
AF XY:
AC XY:
0
AN XY:
46874
African (AFR)
AF:
AC:
0
AN:
22766
American (AMR)
AF:
AC:
0
AN:
8674
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2344
East Asian (EAS)
AF:
AC:
0
AN:
3412
South Asian (SAS)
AF:
AC:
0
AN:
3098
European-Finnish (FIN)
AF:
AC:
0
AN:
6112
Middle Eastern (MID)
AF:
AC:
0
AN:
208
European-Non Finnish (NFE)
AF:
AC:
0
AN:
48900
Other (OTH)
AF:
AC:
0
AN:
1258
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
B;P
Vest4
MutPred
Loss of glycosylation at P71 (P = 0.0986);Loss of glycosylation at P71 (P = 0.0986);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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