rs9282731
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_004970.3(IGFALS):c.1642C>T(p.Arg548Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 1,583,154 control chromosomes in the GnomAD database, including 2,959 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R548Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_004970.3 missense
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IGFALS | NM_004970.3 | c.1642C>T | p.Arg548Trp | missense_variant | 2/2 | ENST00000215539.4 | |
IGFALS | NM_001146006.2 | c.1756C>T | p.Arg586Trp | missense_variant | 2/2 | ||
IGFALS | NR_027389.1 | n.1696C>T | non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IGFALS | ENST00000215539.4 | c.1642C>T | p.Arg548Trp | missense_variant | 2/2 | 1 | NM_004970.3 | P1 | |
IGFALS | ENST00000415638.3 | c.1756C>T | p.Arg586Trp | missense_variant | 2/2 | 2 | |||
SPSB3 | ENST00000569769.1 | c.-13+2861C>T | intron_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0757 AC: 11511AN: 152146Hom.: 1368 Cov.: 33
GnomAD3 exomes AF: 0.0295 AC: 5716AN: 194064Hom.: 492 AF XY: 0.0280 AC XY: 2943AN XY: 105038
GnomAD4 exome AF: 0.0125 AC: 17881AN: 1430892Hom.: 1587 Cov.: 30 AF XY: 0.0136 AC XY: 9649AN XY: 709394
GnomAD4 genome ? AF: 0.0758 AC: 11548AN: 152262Hom.: 1372 Cov.: 33 AF XY: 0.0742 AC XY: 5527AN XY: 74462
ClinVar
Submissions by phenotype
IGFALS-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 06, 2019 | 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). - |
Short stature due to primary acid-labile subunit deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at