rs200268317
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_000484.4(APP):c.1457G>A(p.Arg486Gln) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000254 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000484.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APP | NM_000484.4 | c.1457G>A | p.Arg486Gln | missense_variant, splice_region_variant | 11/18 | ENST00000346798.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APP | ENST00000346798.8 | c.1457G>A | p.Arg486Gln | missense_variant, splice_region_variant | 11/18 | 1 | NM_000484.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152122Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250670Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135550
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461798Hom.: 0 Cov.: 31 AF XY: 0.0000303 AC XY: 22AN XY: 727200
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74434
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 04, 2018 | - - |
Alzheimer disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 11, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 486 of the APP protein (p.Arg486Gln). This variant is present in population databases (rs200268317, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with APP-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 585428). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at