rs199786076
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_017617.5(NOTCH1):c.6083-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000576 in 1,613,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_017617.5 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.6083-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000651671.1 | |||
NOTCH1 | XM_011518717.3 | c.5360-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.6083-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | NM_017617.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152260Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000723 AC: 18AN: 248892Hom.: 0 AF XY: 0.0000887 AC XY: 12AN XY: 135222
GnomAD4 exome AF: 0.0000548 AC: 80AN: 1460866Hom.: 0 Cov.: 32 AF XY: 0.0000592 AC XY: 43AN XY: 726758
GnomAD4 genome ? AF: 0.0000853 AC: 13AN: 152378Hom.: 0 Cov.: 34 AF XY: 0.0000537 AC XY: 4AN XY: 74510
ClinVar
Submissions by phenotype
Adams-Oliver syndrome 5 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 27, 2019 | - - |
Aortic valve disease 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at