rs528033027
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PP2PP3BP6_ModerateBS2
The NM_017617.5(NOTCH1):c.1277C>T(p.Ala426Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000807 in 1,611,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A426G) has been classified as Uncertain significance.
Frequency
Consequence
NM_017617.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.1277C>T | p.Ala426Val | missense_variant | 8/34 | ENST00000651671.1 | |
LOC124902310 | XR_007061865.1 | n.508-5402G>A | intron_variant, non_coding_transcript_variant | ||||
NOTCH1 | XM_011518717.3 | c.554C>T | p.Ala185Val | missense_variant | 5/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.1277C>T | p.Ala426Val | missense_variant | 8/34 | NM_017617.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152054Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000122 AC: 3AN: 246338Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134500
GnomAD4 exome AF: 0.00000822 AC: 12AN: 1459234Hom.: 0 Cov.: 35 AF XY: 0.00000689 AC XY: 5AN XY: 726016
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152054Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1AN XY: 74258
ClinVar
Submissions by phenotype
Adams-Oliver syndrome 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | May 28, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at