rs3812602
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_017617.5(NOTCH1):c.3315G>T(p.Ala1105=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000829 in 1,611,658 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A1105A) 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 -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.3315G>T | p.Ala1105= | synonymous_variant | 20/34 | ENST00000651671.1 | |
NOTCH1 | XM_011518717.3 | c.2592G>T | p.Ala864= | synonymous_variant | 17/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.3315G>T | p.Ala1105= | synonymous_variant | 20/34 | NM_017617.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00122 AC: 186AN: 152146Hom.: 4 Cov.: 34
GnomAD3 exomes AF: 0.00265 AC: 654AN: 246598Hom.: 15 AF XY: 0.00237 AC XY: 318AN XY: 134448
GnomAD4 exome AF: 0.000788 AC: 1150AN: 1459394Hom.: 15 Cov.: 39 AF XY: 0.000718 AC XY: 521AN XY: 725966
GnomAD4 genome ? AF: 0.00122 AC: 186AN: 152264Hom.: 4 Cov.: 34 AF XY: 0.00141 AC XY: 105AN XY: 74438
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 30, 2017 | 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, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:2
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Oct 16, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 04, 2017 | This alteration is classified as 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
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jun 14, 2023 | - - |
Adams-Oliver syndrome 5 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Aortic valve disease 1 Benign:1
Benign, 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