chr8-18057617-C-T
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBS1BS2
The NM_177924.5(ASAH1):c.1105G>A(p.Val369Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00254 in 1,598,538 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_177924.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00405 AC: 616AN: 152130Hom.: 5 Cov.: 32
GnomAD3 exomes AF: 0.00877 AC: 2200AN: 250950Hom.: 43 AF XY: 0.00709 AC XY: 962AN XY: 135618
GnomAD4 exome AF: 0.00238 AC: 3447AN: 1446292Hom.: 45 Cov.: 30 AF XY: 0.00215 AC XY: 1545AN XY: 719872
GnomAD4 genome AF: 0.00407 AC: 619AN: 152246Hom.: 5 Cov.: 32 AF XY: 0.00453 AC XY: 337AN XY: 74434
ClinVar
Submissions by phenotype
not provided Benign:6
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This variant is associated with the following publications: (PMID: 29140481) -
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ASAH1: BP4, BS1, BS2 -
not specified Benign:1
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Farber lipogranulomatosis Benign:1
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. -
ASAH1-related disorders Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at