rs1044116
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000435.3(NOTCH3):c.*808G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 233,580 control chromosomes in the GnomAD database, including 57,716 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.68 ( 36445 hom., cov: 35)
Exomes 𝑓: 0.72 ( 21271 hom. )
Consequence
NOTCH3
NM_000435.3 3_prime_UTR
NM_000435.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.992
Genes affected
NOTCH3 (HGNC:7883): (notch receptor 3) This gene encodes the third discovered human homologue of the Drosophilia melanogaster type I membrane protein notch. In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signalling pathway that plays a key role in neural development. Homologues of the notch-ligands have also been identified in human, but precise interactions between these ligands and the human notch homologues remains to be determined. Mutations in NOTCH3 have been identified as the underlying cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 19-15159854-C-T is Benign according to our data. Variant chr19-15159854-C-T is described in ClinVar as [Benign]. Clinvar id is 328360.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH3 | NM_000435.3 | c.*808G>A | 3_prime_UTR_variant | 33/33 | ENST00000263388.7 | ||
NOTCH3 | XM_005259924.5 | c.*808G>A | 3_prime_UTR_variant | 32/32 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH3 | ENST00000263388.7 | c.*808G>A | 3_prime_UTR_variant | 33/33 | 1 | NM_000435.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.683 AC: 103964AN: 152108Hom.: 36436 Cov.: 35
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GnomAD4 exome AF: 0.718 AC: 58432AN: 81354Hom.: 21271 Cov.: 0 AF XY: 0.723 AC XY: 27107AN XY: 37472
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GnomAD4 genome ? AF: 0.683 AC: 103999AN: 152226Hom.: 36445 Cov.: 35 AF XY: 0.683 AC XY: 50849AN XY: 74424
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at