rs180916492
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_017617.5(NOTCH1):c.5167+228T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 702,880 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0031 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00042 ( 0 hom. )
Consequence
NOTCH1
NM_017617.5 intron
NM_017617.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.12
Genes affected
NOTCH1 (HGNC:7881): (notch receptor 1) This gene encodes a member of the NOTCH family of proteins. Members of this Type I transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain consisting of multiple different domain types. Notch signaling is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells through binding of Notch family receptors to their cognate ligands. The encoded preproprotein is proteolytically processed in the trans-Golgi network to generate two polypeptide chains that heterodimerize to form the mature cell-surface receptor. This receptor plays a role in the development of numerous cell and tissue types. Mutations in this gene are associated with aortic valve disease, Adams-Oliver syndrome, T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and head and neck squamous cell carcinoma. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
?
Variant 9-136502954-A-C is Benign according to our data. Variant chr9-136502954-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 133356.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 475 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.5167+228T>G | intron_variant | ENST00000651671.1 | |||
NOTCH1 | XM_011518717.3 | c.4444+228T>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.5167+228T>G | intron_variant | NM_017617.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00312 AC: 475AN: 152098Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000721 AC: 97AN: 134582Hom.: 0 AF XY: 0.000559 AC XY: 41AN XY: 73296
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GnomAD4 exome AF: 0.000421 AC: 232AN: 550664Hom.: 0 Cov.: 5 AF XY: 0.000364 AC XY: 108AN XY: 297090
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GnomAD4 genome ? AF: 0.00313 AC: 476AN: 152216Hom.: 1 Cov.: 33 AF XY: 0.00318 AC XY: 237AN XY: 74422
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 22, 2018 | - - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at