rs5000803
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_002124.4(HLA-DRB1):c.100+1582A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 133,490 control chromosomes in the GnomAD database, including 28,368 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 0.65 ( 28368 hom., cov: 22)
Consequence
HLA-DRB1
NM_002124.4 intron
NM_002124.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.773
Genes affected
HLA-DRB1 (HGNC:4948): (major histocompatibility complex, class II, DR beta 1) HLA-DRB1 belongs to the HLA class II beta chain paralogs. The class II molecule is a heterodimer consisting of an alpha (DRA) and a beta chain (DRB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells. The beta chain is approximately 26-28 kDa. It is encoded by 6 exons. Exon one encodes the leader peptide; exons 2 and 3 encode the two extracellular domains; exon 4 encodes the transmembrane domain; and exon 5 encodes the cytoplasmic tail. Within the DR molecule the beta chain contains all the polymorphisms specifying the peptide binding specificities. Hundreds of DRB1 alleles have been described and some alleles have increased frequencies associated with certain diseases or conditions. For example, DRB1*1302 has been related to acute and chronic hepatitis B virus persistence. There are multiple pseudogenes of this gene. [provided by RefSeq, Jul 2020]
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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=-0.89).
BA1
?
GnomAd4 highest subpopulation (AMR) 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-DRB1 | NM_002124.4 | c.100+1582A>C | intron_variant | ENST00000360004.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HLA-DRB1 | ENST00000360004.6 | c.100+1582A>C | intron_variant | NM_002124.4 | P1 | ||||
HLA-DRB1 | ENST00000696610.1 | c.100+1582A>C | intron_variant, NMD_transcript_variant | ||||||
HLA-DRB1 | ENST00000696612.1 | n.163+1582A>C | intron_variant, non_coding_transcript_variant | ||||||
HLA-DRB1 | ENST00000696614.1 | n.228+855A>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.648 AC: 86406AN: 133396Hom.: 28361 Cov.: 22
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.648 AC: 86445AN: 133490Hom.: 28368 Cov.: 22 AF XY: 0.645 AC XY: 41738AN XY: 64668
GnomAD4 genome
?
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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