rs78501403
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000435.3(NOTCH3):āc.4679G>Cā(p.Arg1560Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000893 in 1,604,112 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1560Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_000435.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH3 | NM_000435.3 | c.4679G>C | p.Arg1560Pro | missense_variant | 25/33 | ENST00000263388.7 | |
NOTCH3 | XM_005259924.5 | c.4523G>C | p.Arg1508Pro | missense_variant | 24/32 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH3 | ENST00000263388.7 | c.4679G>C | p.Arg1560Pro | missense_variant | 25/33 | 1 | NM_000435.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00459 AC: 699AN: 152250Hom.: 7 Cov.: 32
GnomAD3 exomes AF: 0.00115 AC: 279AN: 242438Hom.: 0 AF XY: 0.000853 AC XY: 113AN XY: 132542
GnomAD4 exome AF: 0.000501 AC: 728AN: 1451744Hom.: 2 Cov.: 30 AF XY: 0.000429 AC XY: 309AN XY: 720518
GnomAD4 genome AF: 0.00462 AC: 704AN: 152368Hom.: 7 Cov.: 32 AF XY: 0.00437 AC XY: 326AN XY: 74518
ClinVar
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 14, 2021 | This variant is associated with the following publications: (PMID: 24086431) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 03, 2023 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 19, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at