rs2293688
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_172341.4(PSENEN):c.62-75C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,225,486 control chromosomes in the GnomAD database, including 77,644 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 0.40 ( 12942 hom., cov: 31)
Exomes 𝑓: 0.34 ( 64702 hom. )
Consequence
PSENEN
NM_172341.4 intron
NM_172341.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.0880
Genes affected
PSENEN (HGNC:30100): (presenilin enhancer, gamma-secretase subunit) Presenilins, which are components of the gamma-secretase protein complex, are required for intramembranous processing of some type I transmembrane proteins, such as the Notch proteins and the beta-amyloid precursor protein. Signaling by Notch receptors mediates a wide range of developmental cell fates. Processing of the beta-amyloid precursor protein generates neurotoxic amyloid beta peptides, the major component of senile plaques associated with Alzheimer's disease. This gene encodes a protein that is required for Notch pathway signaling, and for the activity and accumulation of gamma-secretase. Mutations resulting in haploinsufficiency for this gene cause familial acne inversa-2 (ACNINV2). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
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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=-0.86).
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PSENEN | NM_172341.4 | c.62-75C>G | intron_variant | ENST00000587708.7 | |||
PSENEN | NM_001281532.3 | c.62-75C>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PSENEN | ENST00000587708.7 | c.62-75C>G | intron_variant | 1 | NM_172341.4 | P1 | |||
PSENEN | ENST00000222266.2 | c.62-75C>G | intron_variant | 1 | P1 | ||||
PSENEN | ENST00000591949.1 | c.62-75C>G | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.401 AC: 60842AN: 151778Hom.: 12924 Cov.: 31
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GnomAD4 exome AF: 0.341 AC: 366120AN: 1073590Hom.: 64702 AF XY: 0.343 AC XY: 188911AN XY: 551128
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GnomAD4 genome ? AF: 0.401 AC: 60914AN: 151896Hom.: 12942 Cov.: 31 AF XY: 0.399 AC XY: 29585AN XY: 74220
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ClinVar
Not reported inComputational scores
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Name
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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