rs378352
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1
The NM_002119.4(HLA-DOA):c.672C>T(p.Gly224Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,613,678 control chromosomes in the GnomAD database, including 36,516 homozygotes. 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: 𝑓 0.17 ( 2813 hom., cov: 32)
Exomes 𝑓: 0.21 ( 33703 hom. )
Consequence
HLA-DOA
NM_002119.4 synonymous
NM_002119.4 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.302
Genes affected
HLA-DOA (HGNC:4936): (major histocompatibility complex, class II, DO alpha) HLA-DOA belongs to the HLA class II alpha chain paralogues. HLA-DOA forms a heterodimer with HLA-DOB. The heterodimer, HLA-DO, is found in lysosomes in B cells and regulates HLA-DM-mediated peptide loading on MHC class II molecules. In comparison with classical HLA class II molecules, this gene exhibits very little sequence variation, especially at the protein level. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP7
Synonymous conserved (PhyloP=0.302 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HLA-DOA | NM_002119.4 | c.672C>T | p.Gly224Gly | synonymous_variant | 4/5 | ENST00000229829.7 | NP_002110.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HLA-DOA | ENST00000229829.7 | c.672C>T | p.Gly224Gly | synonymous_variant | 4/5 | 6 | NM_002119.4 | ENSP00000229829.3 | ||
HLA-DOA | ENST00000485901.1 | n.478C>T | non_coding_transcript_exon_variant | 2/3 | 6 | |||||
HLA-DOA | ENST00000490305.5 | n.90C>T | non_coding_transcript_exon_variant | 2/3 | 6 |
Frequencies
GnomAD3 genomes AF: 0.169 AC: 25728AN: 152092Hom.: 2809 Cov.: 32
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GnomAD3 exomes AF: 0.204 AC: 51025AN: 250536Hom.: 6238 AF XY: 0.207 AC XY: 28158AN XY: 135740
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GnomAD4 exome AF: 0.209 AC: 305752AN: 1461468Hom.: 33703 Cov.: 45 AF XY: 0.210 AC XY: 152355AN XY: 727062
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GnomAD4 genome AF: 0.169 AC: 25735AN: 152210Hom.: 2813 Cov.: 32 AF XY: 0.172 AC XY: 12800AN XY: 74420
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at