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GeneBe

15-22870187-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 1P and 11B. PP3BP6_ModerateBP7BS1BS2

The NM_014608.6(CYFIP1):c.3603G>A(p.Leu1201=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,609,202 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0091 ( 21 hom., cov: 33)
Exomes 𝑓: 0.0012 ( 32 hom. )

Consequence

CYFIP1
NM_014608.6 synonymous

Scores

1
1

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.77
Variant links:
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 Benign. Variant got -10 ACMG points.

PP3
?
    PP3 - Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.)
BayesDel_noAF computational evidence supports a deleterious effect, 0.26
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-22870187-C-T is Benign according to our data. Variant chr15-22870187-C-T is described in ClinVar as [Benign]. Clinvar id is 781719.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.77 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00905 (1379/152328) while in subpopulation AFR AF= 0.0303 (1260/41566). AF 95% confidence interval is 0.0289. There are 21 homozygotes in gnomad4. There are 642 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 21 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CYFIP1NM_014608.6 linkuse as main transcriptc.3603G>A p.Leu1201= synonymous_variant 31/31 ENST00000617928.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CYFIP1ENST00000617928.5 linkuse as main transcriptc.3603G>A p.Leu1201= synonymous_variant 31/311 NM_014608.6 P1Q7L576-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00905
AC:
1377
AN:
152210
Hom.:
21
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0303
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00236
Gnomad ASJ
AF:
0.0109
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000426
Gnomad OTH
AF:
0.00717
GnomAD3 exomes
AF:
0.00267
AC:
656
AN:
246036
Hom.:
12
AF XY:
0.00213
AC XY:
284
AN XY:
133178
show subpopulations
Gnomad AFR exome
AF:
0.0296
Gnomad AMR exome
AF:
0.00207
Gnomad ASJ exome
AF:
0.00699
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000338
Gnomad FIN exome
AF:
0.0000464
Gnomad NFE exome
AF:
0.000285
Gnomad OTH exome
AF:
0.00218
GnomAD4 exome
AF:
0.00117
AC:
1711
AN:
1456874
Hom.:
32
Cov.:
31
AF XY:
0.00104
AC XY:
756
AN XY:
724666
show subpopulations
Gnomad4 AFR exome
AF:
0.0310
Gnomad4 AMR exome
AF:
0.00224
Gnomad4 ASJ exome
AF:
0.00687
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000470
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000186
Gnomad4 OTH exome
AF:
0.00299
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00905
AC:
1379
AN:
152328
Hom.:
21
Cov.:
33
AF XY:
0.00862
AC XY:
642
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.0303
Gnomad4 AMR
AF:
0.00235
Gnomad4 ASJ
AF:
0.0109
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000426
Gnomad4 OTH
AF:
0.00710
Alfa
AF:
0.00552
Hom.:
3
Bravo
AF:
0.0102
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Pathogenic
0.26
Cadd
Benign
8.5
Dann
Benign
0.61

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs115512378; hg19: chr15-23002881; API