rs8084
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1
The NM_019111.5(HLA-DRA):āc.402A>Cā(p.Ile134=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 1,611,822 control chromosomes in the GnomAD database, including 277,896 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).
Frequency
Genomes: š 0.59 ( 26922 hom., cov: 30)
Exomes š: 0.58 ( 250974 hom. )
Consequence
HLA-DRA
NM_019111.5 synonymous
NM_019111.5 synonymous
Scores
7
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -3.39
Genes affected
HLA-DRA (HGNC:4947): (major histocompatibility complex, class II, DR alpha) HLA-DRA is one of the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha and a beta chain, both anchored in the membrane. This molecule is expressed on the surface of various antigen presenting cells such as B lymphocytes, dendritic cells, and monocytes/macrophages, and plays a central role in the immune system and response by presenting peptides derived from extracellular proteins, in particular, pathogen-derived peptides to T cells. The alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. DRA does not have polymorphisms in the peptide binding part and acts as the sole alpha chain for DRB1, DRB3, DRB4 and DRB5. [provided by RefSeq, Aug 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_addAF=-0.911607).
BP6
?
Variant 6-32443258-A-C is Benign according to our data. Variant chr6-32443258-A-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-3.39 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HLA-DRA | NM_019111.5 | c.402A>C | p.Ile134= | synonymous_variant | 3/5 | ENST00000395388.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HLA-DRA | ENST00000395388.7 | c.402A>C | p.Ile134= | synonymous_variant | 3/5 | NM_019111.5 | P1 | ||
HLA-DRA | ENST00000374982.5 | c.329-2A>C | splice_acceptor_variant |
Frequencies
GnomAD3 genomes ? AF: 0.592 AC: 89777AN: 151748Hom.: 26903 Cov.: 30
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.611 AC: 150710AN: 246556Hom.: 47059 AF XY: 0.618 AC XY: 83027AN XY: 134378
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GnomAD4 exome AF: 0.582 AC: 850280AN: 1459956Hom.: 250974 Cov.: 44 AF XY: 0.588 AC XY: 426854AN XY: 726322
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GnomAD4 genome ? AF: 0.592 AC: 89839AN: 151866Hom.: 26922 Cov.: 30 AF XY: 0.593 AC XY: 44034AN XY: 74198
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Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
P;P
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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