rs3754048
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000369102.5(C1orf54):c.-150+969G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,994 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 32)
Consequence
C1orf54
ENST00000369102.5 intron
ENST00000369102.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.65
Genes affected
C1orf54 (HGNC:26258): (chromosome 1 open reading frame 54) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]
APH1A (HGNC:29509): (aph-1 homolog A, gamma-secretase subunit) This gene encodes a component of the gamma secretase complex that cleaves integral membrane proteins such as Notch receptors and beta-amyloid precursor protein. The gamma secretase complex contains this gene product, or the paralogous anterior pharynx defective 1 homolog B (APH1B), along with the presenilin, nicastrin, and presenilin enhancer-2 proteins. The precise function of this seven-transmembrane-domain protein is unknown though it is suspected of facilitating the association of nicastrin and presenilin in the gamma secretase complex as well as interacting with substrates of the gamma secretase complex prior to their proteolytic processing. Polymorphisms in a promoter region of this gene have been associated with an increased risk for developing sporadic Alzheimer's disease. Alternative splicing results in multiple protein-coding and non-protein-coding transcript variants. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| LOC124904414 | XM_047438213.1 | c.357-460C>T | intron_variant | Intron 1 of 1 | XP_047294169.1 | |||
| C1orf54 | XM_047430446.1 | c.-150+969G>A | intron_variant | Intron 1 of 7 | XP_047286402.1 | |||
| C1orf54 | XM_047430455.1 | c.-150+969G>A | intron_variant | Intron 1 of 7 | XP_047286411.1 | |||
| C1orf54 | XM_047430461.1 | c.-150+969G>A | intron_variant | Intron 1 of 6 | XP_047286417.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.0000132 AC: 2AN: 151994Hom.: 0 Cov.: 32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome 0.0000132 AC: 2AN: 151994Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74246
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ClinVar
Not reported inComputational scores
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Name
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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