rs369467132
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS2
The NM_017617.5(NOTCH1):c.4828G>T(p.Ala1610Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,582,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_017617.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.4828G>T | p.Ala1610Ser | missense_variant | 26/34 | ENST00000651671.1 | NP_060087.3 | |
NOTCH1 | XM_011518717.3 | c.4105G>T | p.Ala1369Ser | missense_variant | 23/31 | XP_011517019.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.4828G>T | p.Ala1610Ser | missense_variant | 26/34 | NM_017617.5 | ENSP00000498587 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152208Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000101 AC: 2AN: 197694Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 106940
GnomAD4 exome AF: 0.00000280 AC: 4AN: 1430416Hom.: 0 Cov.: 33 AF XY: 0.00000282 AC XY: 2AN XY: 708544
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152208Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74348
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 25, 2022 | The p.A1610S variant (also known as c.4828G>T), located in coding exon 26 of the NOTCH1 gene, results from a G to T substitution at nucleotide position 4828. The alanine at codon 1610 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Adams-Oliver syndrome 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 24, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at