rs200599265
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1
The NM_000246.4(CIITA):c.2892G>A(p.Leu964Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00025 in 1,613,718 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000246.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CIITA | NM_000246.4 | c.2892G>A | p.Leu964Leu | synonymous_variant | Exon 14 of 20 | ENST00000324288.14 | NP_000237.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CIITA | ENST00000324288.14 | c.2892G>A | p.Leu964Leu | synonymous_variant | Exon 14 of 20 | 1 | NM_000246.4 | ENSP00000316328.8 |
Frequencies
GnomAD3 genomes AF: 0.000204 AC: 31AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000247 AC: 62AN: 251428Hom.: 1 AF XY: 0.000243 AC XY: 33AN XY: 135894
GnomAD4 exome AF: 0.000255 AC: 373AN: 1461566Hom.: 1 Cov.: 31 AF XY: 0.000257 AC XY: 187AN XY: 727106
GnomAD4 genome AF: 0.000204 AC: 31AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74320
ClinVar
Submissions by phenotype
MHC class II deficiency Uncertain:1Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
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CIITA-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at