9-136523955-C-T
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_017617.5(NOTCH1):c.165G>A(p.Pro55Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,563,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_017617.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.165G>A | p.Pro55Pro | synonymous_variant | Exon 3 of 34 | ENST00000651671.1 | NP_060087.3 | |
NOTCH1 | XM_011518717.3 | c.20-4390G>A | intron_variant | Intron 1 of 30 | XP_011517019.2 | |||
LOC124902310 | XR_007061865.1 | n.623+522C>T | intron_variant | Intron 2 of 2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000191 AC: 29AN: 152154Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000561 AC: 90AN: 160304Hom.: 0 AF XY: 0.000563 AC XY: 49AN XY: 86982
GnomAD4 exome AF: 0.000157 AC: 222AN: 1411048Hom.: 0 Cov.: 35 AF XY: 0.000159 AC XY: 111AN XY: 697670
GnomAD4 genome AF: 0.000197 AC: 30AN: 152272Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14AN XY: 74464
ClinVar
Submissions by phenotype
not provided Benign:2
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Adams-Oliver syndrome 5 Benign:2
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Familial thoracic aortic aneurysm and aortic dissection Benign:1
This alteration is classified as likely 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. -
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