chr9-136513108-CGTT-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM4_SupportingBS2
The NM_017617.5(NOTCH1):βc.2377_2379delβ(p.Asn793del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,612,788 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β ). Synonymous variant affecting the same amino acid position (i.e. N793N) has been classified as Likely benign.
Frequency
Consequence
NM_017617.5 inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.2377_2379del | p.Asn793del | inframe_deletion | 15/34 | ENST00000651671.1 | |
LOC124902310 | XR_007061865.1 | n.507+3131_507+3133del | intron_variant, non_coding_transcript_variant | ||||
NOTCH1 | XM_011518717.3 | c.1654_1656del | p.Asn552del | inframe_deletion | 12/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.2377_2379del | p.Asn793del | inframe_deletion | 15/34 | NM_017617.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152012Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000241 AC: 6AN: 248484Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135274
GnomAD4 exome AF: 0.0000301 AC: 44AN: 1460776Hom.: 0 AF XY: 0.0000344 AC XY: 25AN XY: 726698
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152012Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74240
ClinVar
Submissions by phenotype
Adams-Oliver syndrome 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 28, 2023 | This variant, c.2377_2379del, results in the deletion of 1 amino acid(s) of the NOTCH1 protein (p.Asn793del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs587778561, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with NOTCH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 134916). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at