15-22874625-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_014608.6(CYFIP1):c.3135C>T(p.Ala1045=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000437 in 1,601,770 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 (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000044 ( 0 hom. )
Consequence
CYFIP1
NM_014608.6 synonymous
NM_014608.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.256
Genes affected
CYFIP1 (HGNC:13759): (cytoplasmic FMR1 interacting protein 1) This gene encodes a protein that regulates cytoskeletal dynamics and protein translation. The encoded protein is a component of the WAVE regulatory complex (WRC), which promotes actin polymerization. This protein also interacts with the synaptic functional regulator FMR1 protein and translation initiation factor 4E to inhibit protein translation. A large chromosomal deletion including this gene is associated with increased risk of schizophrenia and epilepsy in human patients. Reduced expression of this gene has been observed in various human cancers and the encoded protein may inhibit tumor invasion. [provided by RefSeq, Mar 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.26).
BP6
?
Variant 15-22874625-G-A is Benign according to our data. Variant chr15-22874625-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 745079.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.256 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYFIP1 | NM_014608.6 | c.3135C>T | p.Ala1045= | synonymous_variant | 28/31 | ENST00000617928.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYFIP1 | ENST00000617928.5 | c.3135C>T | p.Ala1045= | synonymous_variant | 28/31 | 1 | NM_014608.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152112Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000422 AC: 10AN: 237054Hom.: 0 AF XY: 0.0000389 AC XY: 5AN XY: 128672
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GnomAD4 exome AF: 0.0000442 AC: 64AN: 1449540Hom.: 0 Cov.: 30 AF XY: 0.0000513 AC XY: 37AN XY: 720990
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152230Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74432
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 06, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
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Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at