rs378352
Positions:
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.Gly224=) 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]
Genome browser will be placed here
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 | UniProt |
---|---|---|---|---|---|---|---|
HLA-DOA | NM_002119.4 | c.672C>T | p.Gly224= | synonymous_variant | 4/5 | ENST00000229829.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HLA-DOA | ENST00000229829.7 | c.672C>T | p.Gly224= | synonymous_variant | 4/5 | NM_002119.4 | P1 | ||
HLA-DOA | ENST00000485901.1 | n.478C>T | non_coding_transcript_exon_variant | 2/3 | |||||
HLA-DOA | ENST00000490305.5 | n.90C>T | non_coding_transcript_exon_variant | 2/3 |
Frequencies
GnomAD3 genomes ? AF: 0.169 AC: 25728AN: 152092Hom.: 2809 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
25728
AN:
152092
Hom.:
Cov.:
32
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:
GnomAD3 exomes AF: 0.204 AC: 51025AN: 250536Hom.: 6238 AF XY: 0.207 AC XY: 28158AN XY: 135740
GnomAD3 exomes
AF:
AC:
51025
AN:
250536
Hom.:
AF XY:
AC XY:
28158
AN XY:
135740
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.209 AC: 305752AN: 1461468Hom.: 33703 Cov.: 45 AF XY: 0.210 AC XY: 152355AN XY: 727062
GnomAD4 exome
AF:
AC:
305752
AN:
1461468
Hom.:
Cov.:
45
AF XY:
AC XY:
152355
AN XY:
727062
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.169 AC: 25735AN: 152210Hom.: 2813 Cov.: 32 AF XY: 0.172 AC XY: 12800AN XY: 74420
GnomAD4 genome
?
AF:
AC:
25735
AN:
152210
Hom.:
Cov.:
32
AF XY:
AC XY:
12800
AN XY:
74420
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
755
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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