rs139863395
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The ENST00000324501.10(PSEN1):āc.321C>Gā(p.Thr107=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000256 in 1,614,120 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 Benign (ā ā ).
Frequency
Genomes: š 0.0014 ( 0 hom., cov: 32)
Exomes š: 0.00014 ( 0 hom. )
Consequence
PSEN1
ENST00000324501.10 synonymous
ENST00000324501.10 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.541
Genes affected
PSEN1 (HGNC:9508): (presenilin 1) Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1; PSEN2) or in the amyloid precursor protein (APP). These disease-linked mutations result in increased production of the longer form of amyloid-beta (main component of amyloid deposits found in AD brains). Presenilins are postulated to regulate APP processing through their effects on gamma-secretase, an enzyme that cleaves APP. Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor, such that they either directly regulate gamma-secretase activity or themselves are protease enzymes. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene, the full-length nature of only some have been determined. [provided by RefSeq, Aug 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
Variant 14-73171030-C-G is Benign according to our data. Variant chr14-73171030-C-G is described in ClinVar as [Benign]. Clinvar id is 586383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.541 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00139 (211/152248) while in subpopulation AFR AF= 0.00489 (203/41544). AF 95% confidence interval is 0.00434. There are 0 homozygotes in gnomad4. There are 96 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 211 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PSEN1 | NM_000021.4 | c.321C>G | p.Thr107= | synonymous_variant | 4/12 | ENST00000324501.10 | NP_000012.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PSEN1 | ENST00000324501.10 | c.321C>G | p.Thr107= | synonymous_variant | 4/12 | 1 | NM_000021.4 | ENSP00000326366 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00138 AC: 210AN: 152130Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000382 AC: 96AN: 251440Hom.: 0 AF XY: 0.000243 AC XY: 33AN XY: 135890
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GnomAD4 exome AF: 0.000139 AC: 203AN: 1461872Hom.: 0 Cov.: 32 AF XY: 0.000120 AC XY: 87AN XY: 727232
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GnomAD4 genome AF: 0.00139 AC: 211AN: 152248Hom.: 0 Cov.: 32 AF XY: 0.00129 AC XY: 96AN XY: 74434
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Pick disease;C0338451:Frontotemporal dementia;C1843013:Alzheimer disease 3;C3151038:Acne inversa, familial, 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 25, 2023 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 30, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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