9-136497025-G-A
Variant summary
Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_017617.5(NOTCH1):c.6714C>T(p.Pro2238Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000652 in 1,609,436 control chromosomes in the GnomAD database, including 1 homozygotes. 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
Genome browser will be placed here
ACMG classification
Our verdict: Benign. The variant received -21 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152174Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.000196 AC: 48AN: 244300 AF XY: 0.000157 show subpopulations
GnomAD4 exome AF: 0.0000631 AC: 92AN: 1457144Hom.: 1 Cov.: 32 AF XY: 0.0000607 AC XY: 44AN XY: 724502 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152292Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5AN XY: 74472 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Benign:2
- -
NOTCH1: BP4, BP7 -
Adams-Oliver syndrome 5 Benign:2
- -
- -
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. -
Aortic valve disease 1 Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at