9-136502057-T-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_017617.5(NOTCH1):āc.5416A>Gā(p.Met1806Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,613,332 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M1806I) has been classified as Uncertain significance.
Frequency
Consequence
NM_017617.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.5416A>G | p.Met1806Val | missense_variant | 29/34 | ENST00000651671.1 | |
NOTCH1 | XM_011518717.3 | c.4693A>G | p.Met1565Val | missense_variant | 26/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.5416A>G | p.Met1806Val | missense_variant | 29/34 | NM_017617.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152132Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000804 AC: 2AN: 248646Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135192
GnomAD4 exome AF: 0.00000890 AC: 13AN: 1461082Hom.: 0 Cov.: 35 AF XY: 0.00000963 AC XY: 7AN XY: 726824
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152250Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74440
ClinVar
Submissions by phenotype
Adams-Oliver syndrome 5 Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Dec 22, 2020 | - - |
Aortic valve disease 1;C4014970:Adams-Oliver syndrome 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 23, 2021 | - - |
Aortic valve disease 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at