rs777859108
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PP2PP3_ModerateBP6_ModerateBS2
The NM_017617.5(NOTCH1):c.5272C>T(p.Arg1758Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000685 in 1,459,876 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1758H) has been classified as Likely benign.
Frequency
Consequence
NM_017617.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.5272C>T | p.Arg1758Cys | missense_variant | 28/34 | ENST00000651671.1 | |
NOTCH1 | XM_011518717.3 | c.4549C>T | p.Arg1517Cys | missense_variant | 25/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.5272C>T | p.Arg1758Cys | missense_variant | 28/34 | NM_017617.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000831 AC: 2AN: 240680Hom.: 0 AF XY: 0.00000755 AC XY: 1AN XY: 132492
GnomAD4 exome AF: 0.00000685 AC: 10AN: 1459876Hom.: 0 Cov.: 32 AF XY: 0.00000826 AC XY: 6AN XY: 726268
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Adams-Oliver syndrome 5 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 07, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at