rs145564988
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_000484.4(APP):c.2148C>T(p.Ile716=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,613,906 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. I716I) has been classified as Benign.
Frequency
Consequence
NM_000484.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APP | NM_000484.4 | c.2148C>T | p.Ile716= | synonymous_variant | 17/18 | ENST00000346798.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APP | ENST00000346798.8 | c.2148C>T | p.Ile716= | synonymous_variant | 17/18 | 1 | NM_000484.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152110Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000796 AC: 20AN: 251364Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135858
GnomAD4 exome AF: 0.000202 AC: 296AN: 1461796Hom.: 0 Cov.: 32 AF XY: 0.000199 AC XY: 145AN XY: 727216
GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152110Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74302
ClinVar
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 12, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2022 | APP: BP4, BP7 - |
Alzheimer disease type 1;C2751536:Cerebral amyloid angiopathy, APP-related Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 27, 2021 | - - |
APP-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 18, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Alzheimer disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 14, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at