chr9-136522890-G-A
Variant summary
Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_017617.5(NOTCH1):c.702C>T(p.Arg234Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,381,392 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 Likely benign (★★).
Frequency
Consequence
NM_017617.5 synonymous
Scores
Clinical Significance
Conservation
Publications
- Adams-Oliver syndromeInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Illumina, Orphanet
- Adams-Oliver syndrome 5Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
- aortic valve disease 1Inheritance: AD Classification: STRONG Submitted by: G2P, PanelApp Australia
- connective tissue disorderInheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
- leukodystrophyInheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
- familial bicuspid aortic valveInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- familial thoracic aortic aneurysm and aortic dissectionInheritance: AD Classification: LIMITED Submitted by: ClinGen
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ACMG classification
Our verdict: Benign. The variant received -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.702C>T | p.Arg234Arg | synonymous_variant | Exon 4 of 34 | ENST00000651671.1 | NP_060087.3 | |
NOTCH1 | XM_011518717.3 | c.20-3325C>T | intron_variant | Intron 1 of 30 | XP_011517019.2 | |||
LOC124902310 | XR_007061865.1 | n.508-428G>A | intron_variant | Intron 1 of 2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD2 exomes AF: 0.0000557 AC: 8AN: 143604 AF XY: 0.0000129 show subpopulations
GnomAD4 exome AF: 0.00000434 AC: 6AN: 1381392Hom.: 0 Cov.: 31 AF XY: 0.00000147 AC XY: 1AN XY: 678962 show subpopulations
Age Distribution
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Benign:1
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. -
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