16-10930248-C-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000246.4(CIITA):c.*6393C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 152,152 control chromosomes in the GnomAD database, including 14,917 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 0.41 ( 14910 hom., cov: 32)
Exomes 𝑓: 0.46 ( 7 hom. )
Consequence
CIITA
NM_000246.4 3_prime_UTR
NM_000246.4 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.508
Genes affected
CIITA (HGNC:7067): (class II major histocompatibility complex transactivator) This gene encodes a protein with an acidic transcriptional activation domain, 4 LRRs (leucine-rich repeats) and a GTP binding domain. The protein is located in the nucleus and acts as a positive regulator of class II major histocompatibility complex gene transcription, and is referred to as the "master control factor" for the expression of these genes. The protein also binds GTP and uses GTP binding to facilitate its own transport into the nucleus. Once in the nucleus it does not bind DNA but rather uses an intrinsic acetyltransferase (AT) activity to act in a coactivator-like fashion. Mutations in this gene have been associated with bare lymphocyte syndrome type II (also known as hereditary MHC class II deficiency or HLA class II-deficient combined immunodeficiency), increased susceptibility to rheumatoid arthritis, multiple sclerosis, and possibly myocardial infarction. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]
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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=-0.84).
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CIITA | NM_000246.4 | c.*6393C>T | 3_prime_UTR_variant | 20/20 | ENST00000324288.14 | ||
DEXI | NM_014015.4 | c.*150-689G>A | intron_variant | ENST00000331808.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CIITA | ENST00000324288.14 | c.*6393C>T | 3_prime_UTR_variant | 20/20 | 1 | NM_000246.4 | P4 | ||
DEXI | ENST00000331808.5 | c.*150-689G>A | intron_variant | 1 | NM_014015.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.415 AC: 63102AN: 151958Hom.: 14915 Cov.: 32
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GnomAD4 exome AF: 0.459 AC: 34AN: 74Hom.: 7 Cov.: 0 AF XY: 0.423 AC XY: 22AN XY: 52
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GnomAD4 genome ? AF: 0.415 AC: 63107AN: 152078Hom.: 14910 Cov.: 32 AF XY: 0.421 AC XY: 31272AN XY: 74316
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at