21-44286024-G-C
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The ENST00000291582.6(AIRE):āc.18G>Cā(p.Ala6Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000261 in 1,533,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 33)
Exomes š: 7.2e-7 ( 0 hom. )
Consequence
AIRE
ENST00000291582.6 synonymous
ENST00000291582.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.23
Genes affected
AIRE (HGNC:360): (autoimmune regulator) This gene encodes a transcriptional regulator that forms nuclear bodies and interacts with the transcriptional coactivator CREB binding protein. The encoded protein plays an important role in immunity by regulating the expression of autoantigens and negative selection of autoreactive T-cells in the thymus. Mutations in this gene cause the rare autosomal-recessive systemic autoimmune disease termed autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy (APECED). [provided by RefSeq, Jun 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 21-44286024-G-C is Benign according to our data. Variant chr21-44286024-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 708862.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.23 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AIRE | NM_000383.4 | c.18G>C | p.Ala6Ala | synonymous_variant | 1/14 | ENST00000291582.6 | NP_000374.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AIRE | ENST00000291582.6 | c.18G>C | p.Ala6Ala | synonymous_variant | 1/14 | 1 | NM_000383.4 | ENSP00000291582.5 | ||
AIRE | ENST00000527919.5 | n.179G>C | non_coding_transcript_exon_variant | 1/14 | 2 | |||||
AIRE | ENST00000530812.5 | n.187G>C | non_coding_transcript_exon_variant | 1/12 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152124Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 7.24e-7 AC: 1AN: 1381664Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 681560
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152124Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74314
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Polyglandular autoimmune syndrome, type 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 23, 2020 | - - |
Computational scores
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Benign
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Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at