rs2293452
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_017439.4(GSAP):c.1766-1049C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,346 control chromosomes in the GnomAD database, including 9,105 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 0.34 ( 9086 hom., cov: 32)
Exomes 𝑓: 0.32 ( 19 hom. )
Consequence
GSAP
NM_017439.4 intron
NM_017439.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.132
Genes affected
GSAP (HGNC:28042): (gamma-secretase activating protein) Accumulation of neurotoxic amyloid-beta is a major hallmark of Alzheimer disease (AD; MIM 104300). Formation of amyloid-beta is catalyzed by gamma-secretase (see PSEN1; MIM 104311), a protease with numerous substrates. PION, or GSAP, selectively increases amyloid-beta production through a mechanism involving its interaction with both gamma-secretase and its substrate, the amyloid-beta precursor protein (APP; MIM 104760) C-terminal fragment (APP-CTF) (He et al., 2010 [PubMed 20811458]).[supplied by OMIM, Nov 2010]
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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=-0.87).
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GSAP | NM_017439.4 | c.1766-1049C>T | intron_variant | ENST00000257626.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GSAP | ENST00000257626.12 | c.1766-1049C>T | intron_variant | 1 | NM_017439.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.335 AC: 50971AN: 151944Hom.: 9054 Cov.: 32
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GnomAD4 exome AF: 0.324 AC: 92AN: 284Hom.: 19 Cov.: 0 AF XY: 0.327 AC XY: 66AN XY: 202
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GnomAD4 genome ? AF: 0.336 AC: 51056AN: 152062Hom.: 9086 Cov.: 32 AF XY: 0.338 AC XY: 25149AN XY: 74340
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3478
ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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