chr19-42272208-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001386298.1(CIC):c.425G>A(p.Arg142Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000201 in 398,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001386298.1 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CIC | NM_001386298.1 | c.425G>A | p.Arg142Gln | missense_variant | 2/21 | ENST00000681038.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CIC | ENST00000681038.1 | c.425G>A | p.Arg142Gln | missense_variant | 2/21 | NM_001386298.1 | P1 | ||
CIC | ENST00000572681.6 | c.425G>A | p.Arg142Gln | missense_variant | 2/21 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152182Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000203 AC: 5AN: 246370Hom.: 0 Cov.: 0 AF XY: 0.0000160 AC XY: 2AN XY: 124888
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74338
ClinVar
Submissions by phenotype
Intellectual disability, autosomal dominant 45 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Jun 12, 2020 | The inherited c.425G>A (p.Arg142Gln) variant identified in the CIC gene substitutes a moderately conserved Arginine for Glutamine at amino acid 142/2518 (coding exon 2/21), however several mammalian species including Baboon contain a Glutamine at this amino acid position. This variant is found with low frequency in gnomAD(v3.0) (3 heterozygotes, 0 homozygotes; allele frequency: 2.09e-5) suggesting it is not a common benign variantin the populations represented in that database. In silico algorithms do not agree on the effectof this variant, as it is predicted both Neutral (SIFT; score:0.00) and Damaging (FATHMM; score:-4.9) to the function of the canonical transcript. This variantis absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature. The p.Arg142 reside is not within a mapped domain of CIC (UniProtKB:Q96RK0). Given the lack of compelling evidence for its pathogenicity, the inherited c.425G>A (p.Arg142Gln) variant identified in the CIC gene reported here as aVariant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at