rs6427515
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_015331.3(NCSTN):c.1353-334C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,164 control chromosomes in the GnomAD database, including 8,312 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.22 ( 8312 hom., cov: 32)
Consequence
NCSTN
NM_015331.3 intron
NM_015331.3 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -3.23
Genes affected
NCSTN (HGNC:17091): (nicastrin) This gene encodes a type I transmembrane glycoprotein that is an integral component of the multimeric gamma-secretase complex. The encoded protein cleaves integral membrane proteins, including Notch receptors and beta-amyloid precursor protein, and may be a stabilizing cofactor required for gamma-secretase complex assembly. The cleavage of beta-amyloid precursor protein yields amyloid beta peptide, the main component of the neuritic plaque and the hallmark lesion in the brains of patients with Alzheimer's disease; however, the nature of the encoded protein's role in Alzheimer's disease is not known for certain. Mutations in this gene are associated with familial acne inversa. A pseudogene of this gene is present on chromosome 21. Alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Feb 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NCSTN | NM_015331.3 | c.1353-334C>T | intron_variant | ENST00000294785.10 | |||
NCSTN | NM_001290184.2 | c.1293-334C>T | intron_variant | ||||
NCSTN | NM_001290186.2 | c.939-334C>T | intron_variant | ||||
NCSTN | NM_001349729.2 | c.1353-334C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NCSTN | ENST00000294785.10 | c.1353-334C>T | intron_variant | 1 | NM_015331.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.224 AC: 34119AN: 152046Hom.: 8277 Cov.: 32
GnomAD3 genomes
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.225 AC: 34214AN: 152164Hom.: 8312 Cov.: 32 AF XY: 0.219 AC XY: 16306AN XY: 74414
GnomAD4 genome
?
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34214
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32
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16306
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74414
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514
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3478
ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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Prediction
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