rs399604
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_002119.4(HLA-DOA):c.614-22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,612,856 control chromosomes in the GnomAD database, including 143,870 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 0.40 ( 12293 hom., cov: 32)
Exomes 𝑓: 0.42 ( 131577 hom. )
Consequence
HLA-DOA
NM_002119.4 intron
NM_002119.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -2.17
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 -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HLA-DOA | NM_002119.4 | c.614-22A>G | intron_variant | ENST00000229829.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HLA-DOA | ENST00000229829.7 | c.614-22A>G | intron_variant | NM_002119.4 | P1 | ||||
HLA-DOA | ENST00000485901.1 | n.398A>G | non_coding_transcript_exon_variant | 2/3 | |||||
HLA-DOA | ENST00000490305.5 | n.32-22A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.398 AC: 60456AN: 151868Hom.: 12282 Cov.: 32
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GnomAD3 exomes AF: 0.397 AC: 99000AN: 249256Hom.: 21085 AF XY: 0.402 AC XY: 54462AN XY: 135346
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GnomAD4 exome AF: 0.420 AC: 614265AN: 1460870Hom.: 131577 Cov.: 47 AF XY: 0.420 AC XY: 304965AN XY: 726772
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GnomAD4 genome ? AF: 0.398 AC: 60509AN: 151986Hom.: 12293 Cov.: 32 AF XY: 0.399 AC XY: 29651AN XY: 74288
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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
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