rs587778207
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001386298.1(CIC):c.6683C>T(p.Pro2228Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,612,732 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P2228R) has been classified as Uncertain significance.
Frequency
Consequence
NM_001386298.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CIC | NM_001386298.1 | c.6683C>T | p.Pro2228Leu | missense_variant | 17/21 | ENST00000681038.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CIC | ENST00000681038.1 | c.6683C>T | p.Pro2228Leu | missense_variant | 17/21 | NM_001386298.1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152242Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000164 AC: 4AN: 243282Hom.: 0 AF XY: 0.00000753 AC XY: 1AN XY: 132806
GnomAD4 exome AF: 0.0000199 AC: 29AN: 1460490Hom.: 0 Cov.: 33 AF XY: 0.0000151 AC XY: 11AN XY: 726542
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74368
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 16, 2023 | The c.3956C>T (p.P1319L) alteration is located in exon 16 (coding exon 16) of the CIC gene. This alteration results from a C to T substitution at nucleotide position 3956, causing the proline (P) at amino acid position 1319 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at