chr9-136514668-C-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2
The NM_017617.5(NOTCH1):c.2049G>A(p.Ala683=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,612,312 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A683A) has been classified as Likely benign.
Frequency
Consequence
NM_017617.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.2049G>A | p.Ala683= | synonymous_variant | 13/34 | ENST00000651671.1 | |
LOC124902310 | XR_007061865.1 | n.507+4689C>T | intron_variant, non_coding_transcript_variant | ||||
NOTCH1 | XM_011518717.3 | c.1326G>A | p.Ala442= | synonymous_variant | 10/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.2049G>A | p.Ala683= | synonymous_variant | 13/34 | NM_017617.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000940 AC: 143AN: 152096Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00100 AC: 246AN: 244950Hom.: 0 AF XY: 0.000972 AC XY: 130AN XY: 133696
GnomAD4 exome AF: 0.00114 AC: 1662AN: 1460098Hom.: 2 Cov.: 33 AF XY: 0.00117 AC XY: 848AN XY: 726324
GnomAD4 genome ? AF: 0.000939 AC: 143AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.000833 AC XY: 62AN XY: 74418
ClinVar
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2022 | NOTCH1: BS1 - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 28, 2023 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 20, 2018 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 10, 2023 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 05, 2015 | 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. - |
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Aug 24, 2017 | - - |
Adams-Oliver syndrome 5 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
NOTCH1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 30, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Aortic valve disease 1;C4014970:Adams-Oliver syndrome 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 16, 2022 | - - |
Aortic valve disease 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Connective tissue disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Nov 01, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at