rs10402601
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_172341.4(PSENEN):c.61+17G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 1,612,446 control chromosomes in the GnomAD database, including 19,635 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.14 ( 1628 hom., cov: 32)
Exomes 𝑓: 0.15 ( 18007 hom. )
Consequence
PSENEN
NM_172341.4 intron
NM_172341.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.10
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 19-35746008-G-C is Benign according to our data. Variant chr19-35746008-G-C is described in ClinVar as [Benign]. Clinvar id is 518298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-35746008-G-C is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PSENEN | NM_172341.4 | c.61+17G>C | intron_variant | ENST00000587708.7 | |||
PSENEN | NM_001281532.3 | c.61+17G>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PSENEN | ENST00000587708.7 | c.61+17G>C | intron_variant | 1 | NM_172341.4 | P1 | |||
PSENEN | ENST00000222266.2 | c.61+17G>C | intron_variant | 1 | P1 | ||||
PSENEN | ENST00000591949.1 | c.61+17G>C | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.141 AC: 21414AN: 152090Hom.: 1627 Cov.: 32
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GnomAD3 exomes AF: 0.159 AC: 39857AN: 250718Hom.: 3487 AF XY: 0.165 AC XY: 22340AN XY: 135660
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GnomAD4 exome AF: 0.152 AC: 221411AN: 1460238Hom.: 18007 Cov.: 32 AF XY: 0.154 AC XY: 112222AN XY: 726448
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GnomAD4 genome ? AF: 0.141 AC: 21426AN: 152208Hom.: 1628 Cov.: 32 AF XY: 0.139 AC XY: 10353AN XY: 74432
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Acne inversa, familial, 2 Benign:4
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Oct 25, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Sep 21, 2015 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | Jan 15, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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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