rs749374016
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_017617.5(NOTCH1):c.1863C>T(p.Arg621Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,611,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_017617.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.1863C>T | p.Arg621Arg | synonymous_variant | Exon 11 of 34 | ENST00000651671.1 | NP_060087.3 | |
NOTCH1 | XM_011518717.3 | c.1140C>T | p.Arg380Arg | synonymous_variant | Exon 8 of 31 | XP_011517019.2 | ||
LOC124902310 | XR_007061865.1 | n.507+5544G>A | intron_variant | Intron 1 of 2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152164Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000408 AC: 10AN: 245236Hom.: 0 AF XY: 0.0000672 AC XY: 9AN XY: 133898
GnomAD4 exome AF: 0.0000473 AC: 69AN: 1459582Hom.: 0 Cov.: 34 AF XY: 0.0000496 AC XY: 36AN XY: 726186
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152282Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74448
ClinVar
Submissions by phenotype
not provided Benign:3
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Familial thoracic aortic aneurysm and aortic dissection Benign:2
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This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
not specified Benign:1
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Adams-Oliver syndrome 5 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at