rs9984764
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The ENST00000346798.8(APP):c.58-13034C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 152,260 control chromosomes in the GnomAD database, including 19 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 0.011 ( 19 hom., cov: 32)
Consequence
APP
ENST00000346798.8 intron
ENST00000346798.8 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.171
Genes affected
APP (HGNC:620): (amyloid beta precursor protein) This gene encodes a cell surface receptor and transmembrane precursor protein that is cleaved by secretases to form a number of peptides. Some of these peptides are secreted and can bind to the acetyltransferase complex APBB1/TIP60 to promote transcriptional activation, while others form the protein basis of the amyloid plaques found in the brains of patients with Alzheimer disease. In addition, two of the peptides are antimicrobial peptides, having been shown to have bacteriocidal and antifungal activities. Mutations in this gene have been implicated in autosomal dominant Alzheimer disease and cerebroarterial amyloidosis (cerebral amyloid angiopathy). Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Aug 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=-0.85).
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0106 (1615/152260) while in subpopulation AFR AF= 0.0348 (1444/41522). AF 95% confidence interval is 0.0333. There are 19 homozygotes in gnomad4. There are 791 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1615 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
APP | NM_000484.4 | c.58-13034C>T | intron_variant | ENST00000346798.8 | NP_000475.1 | |||
LOC124900466 | XR_007067829.1 | n.8004-2198C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
APP | ENST00000346798.8 | c.58-13034C>T | intron_variant | 1 | NM_000484.4 | ENSP00000284981 |
Frequencies
GnomAD3 genomes AF: 0.0106 AC: 1608AN: 152142Hom.: 19 Cov.: 32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome AF: 0.0106 AC: 1615AN: 152260Hom.: 19 Cov.: 32 AF XY: 0.0106 AC XY: 791AN XY: 74460
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14
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3478
ClinVar
Not reported inComputational scores
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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