18-23586365-T-G
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000271.5(NPC1):c.-22A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0353 in 1,531,550 control chromosomes in the GnomAD database, including 4,630 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000271.5 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NPC1 | NM_000271.5 | c.-22A>C | 5_prime_UTR_variant | Exon 1 of 25 | ENST00000269228.10 | NP_000262.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0890 AC: 13542AN: 152176Hom.: 1424 Cov.: 33
GnomAD3 exomes AF: 0.0681 AC: 8680AN: 127468Hom.: 818 AF XY: 0.0661 AC XY: 4625AN XY: 69964
GnomAD4 exome AF: 0.0293 AC: 40469AN: 1379258Hom.: 3206 Cov.: 31 AF XY: 0.0305 AC XY: 20778AN XY: 680616
GnomAD4 genome AF: 0.0890 AC: 13560AN: 152292Hom.: 1424 Cov.: 33 AF XY: 0.0883 AC XY: 6579AN XY: 74472
ClinVar
Submissions by phenotype
not provided Benign:3
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Niemann-Pick disease, type C1 Benign:2
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This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not specified Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at