rs116476753
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_014989.7(RIMS1):c.743C>T(p.Ser248Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00667 in 1,607,778 control chromosomes in the GnomAD database, including 291 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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. S248W) has been classified as Uncertain significance.
Frequency
Consequence
NM_014989.7 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 |
---|---|---|---|---|---|---|---|
RIMS1 | NM_014989.7 | c.743C>T | p.Ser248Leu | missense_variant | 5/34 | ENST00000521978.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RIMS1 | ENST00000521978.6 | c.743C>T | p.Ser248Leu | missense_variant | 5/34 | 1 | NM_014989.7 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0162 AC: 2472AN: 152138Hom.: 65 Cov.: 32
GnomAD3 exomes AF: 0.0135 AC: 3270AN: 242458Hom.: 88 AF XY: 0.0145 AC XY: 1909AN XY: 131642
GnomAD4 exome AF: 0.00567 AC: 8248AN: 1455522Hom.: 226 Cov.: 33 AF XY: 0.00672 AC XY: 4865AN XY: 723608
GnomAD4 genome ? AF: 0.0163 AC: 2481AN: 152256Hom.: 65 Cov.: 32 AF XY: 0.0172 AC XY: 1284AN XY: 74436
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 18, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Cone-rod dystrophy 7 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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