chr9-136505829-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4BP6_ModerateBS2
The NM_017617.5(NOTCH1):c.4067G>A(p.Arg1356His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000879 in 1,591,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1356C) 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 -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.4067G>A | p.Arg1356His | missense_variant | 25/34 | ENST00000651671.1 | |
NOTCH1 | XM_011518717.3 | c.3344G>A | p.Arg1115His | missense_variant | 22/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.4067G>A | p.Arg1356His | missense_variant | 25/34 | NM_017617.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000183 AC: 4AN: 218490Hom.: 0 AF XY: 0.0000164 AC XY: 2AN XY: 121858
GnomAD4 exome AF: 0.00000903 AC: 13AN: 1439670Hom.: 0 Cov.: 33 AF XY: 0.0000112 AC XY: 8AN XY: 715768
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74348
ClinVar
Submissions by phenotype
Adams-Oliver syndrome 5 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at