chr8-58491633-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000780.4(CYP7A1):c.1357G>A(p.Glu453Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000477 in 1,614,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000780.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152134Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000835 AC: 21AN: 251366Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135886
GnomAD4 exome AF: 0.0000472 AC: 69AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.0000550 AC XY: 40AN XY: 727242
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74306
ClinVar
Submissions by phenotype
not provided Uncertain:2
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 453 of the CYP7A1 protein (p.Glu453Lys). This variant is present in population databases (rs755342899, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CYP7A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 290137). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt CYP7A1 protein function with a positive predictive value of 80%. 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. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at