9-136515687-T-C
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_017617.5(NOTCH1):āc.1699A>Gā(p.Ile567Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,552,646 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.1699A>G | p.Ile567Val | missense_variant | Exon 11 of 34 | ENST00000651671.1 | NP_060087.3 | |
NOTCH1 | XM_011518717.3 | c.976A>G | p.Ile326Val | missense_variant | Exon 8 of 31 | XP_011517019.2 | ||
LOC124902310 | XR_007061865.1 | n.507+5708T>C | intron_variant | Intron 1 of 2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000164 AC: 25AN: 152176Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000364 AC: 57AN: 156768Hom.: 0 AF XY: 0.000389 AC XY: 33AN XY: 84750
GnomAD4 exome AF: 0.0000964 AC: 135AN: 1400352Hom.: 1 Cov.: 34 AF XY: 0.000127 AC XY: 88AN XY: 692620
GnomAD4 genome AF: 0.000164 AC: 25AN: 152294Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74464
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Benign:2
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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. -
not provided Benign:2
NOTCH1: PP2, BS1, BS2 -
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. -
not specified Benign:1Other:1
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Aortic valve disease 1;C4014970:Adams-Oliver syndrome 5 Uncertain:1
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Adams-Oliver syndrome 5 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at