15-74338027-T-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_000781.3(CYP11A1):āc.1511A>Cā(p.Glu504Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000173 in 1,614,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_000781.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYP11A1 | NM_000781.3 | c.1511A>C | p.Glu504Ala | missense_variant | Exon 9 of 9 | ENST00000268053.11 | NP_000772.2 | |
CYP11A1 | NM_001099773.2 | c.1037A>C | p.Glu346Ala | missense_variant | Exon 9 of 9 | NP_001093243.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251482Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135910
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461862Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727232
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74356
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 504 of the CYP11A1 protein (p.Glu504Ala). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CYP11A1-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CYP11A1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at