rs11574872
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_017617.5(NOTCH1):c.663C>T(p.Pro221Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,551,300 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_017617.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.663C>T | p.Pro221Pro | synonymous_variant | Exon 4 of 34 | ENST00000651671.1 | NP_060087.3 | |
NOTCH1 | XM_011518717.3 | c.20-3364C>T | intron_variant | Intron 1 of 30 | XP_011517019.2 | |||
LOC124902310 | XR_007061865.1 | n.508-389G>A | intron_variant | Intron 1 of 2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00632 AC: 962AN: 152244Hom.: 10 Cov.: 34
GnomAD3 exomes AF: 0.00147 AC: 228AN: 154790Hom.: 0 AF XY: 0.00110 AC XY: 92AN XY: 83402
GnomAD4 exome AF: 0.000699 AC: 978AN: 1398938Hom.: 5 Cov.: 31 AF XY: 0.000592 AC XY: 408AN XY: 689700
GnomAD4 genome AF: 0.00633 AC: 964AN: 152362Hom.: 10 Cov.: 34 AF XY: 0.00579 AC XY: 431AN XY: 74498
ClinVar
Submissions by phenotype
not specified Benign:2
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Familial thoracic aortic aneurysm and aortic dissection Benign:2
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
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Adams-Oliver syndrome 5 Benign:2
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not provided Benign:1
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Aortic valve disease 1 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at