rs1050384
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP7
The NM_002117.6(HLA-C):āc.387C>Gā(p.Pro129=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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: š 0.0019 ( 1 hom., cov: 6)
Exomes š: 0.0073 ( 287 hom. )
Failed GnomAD Quality Control
Consequence
HLA-C
NM_002117.6 synonymous
NM_002117.6 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -6.48
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BP7
?
Synonymous conserved (PhyloP=-6.48 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HLA-C | NM_002117.6 | c.387C>G | p.Pro129= | synonymous_variant | 3/8 | ENST00000376228.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HLA-C | ENST00000376228.10 | c.387C>G | p.Pro129= | synonymous_variant | 3/8 | NM_002117.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00194 AC: 121AN: 62276Hom.: 1 Cov.: 6
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GnomAD3 exomes AF: 0.141 AC: 31387AN: 222356Hom.: 331 AF XY: 0.138 AC XY: 16781AN XY: 121466
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00729 AC: 7209AN: 988374Hom.: 287 Cov.: 28 AF XY: 0.00795 AC XY: 3941AN XY: 495880
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GnomAD4 genome ? AF: 0.00193 AC: 120AN: 62308Hom.: 1 Cov.: 6 AF XY: 0.00195 AC XY: 58AN XY: 29720
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ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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