9-136504720-G-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_017617.5(NOTCH1):āc.4971C>Gā(p.Ser1657Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000759 in 1,540,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
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
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152170Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000980 AC: 14AN: 142798Hom.: 0 AF XY: 0.0000520 AC XY: 4AN XY: 76984
GnomAD4 exome AF: 0.0000807 AC: 112AN: 1388518Hom.: 0 Cov.: 33 AF XY: 0.0000702 AC XY: 48AN XY: 683652
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152170Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74332
ClinVar
Submissions by phenotype
Adams-Oliver syndrome 5 Uncertain:1Benign:1
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Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
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not provided Uncertain:1
Has been reported as a likely benign variant in an individual with bicuspid aortic valve in published literature (PMID: 26820064); In silico analysis supports a deleterious effect on splicing; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26820064) -
Aortic valve disease 1 Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at