15-22939377-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014608.6(CYFIP1):​c.666+34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,613,528 control chromosomes in the GnomAD database, including 63,651 homozygotes. 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 0.24 ( 4764 hom., cov: 30)
Exomes 𝑓: 0.28 ( 58887 hom. )

Consequence

CYFIP1
NM_014608.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0780
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CYFIP1NM_014608.6 linkuse as main transcriptc.666+34G>A intron_variant ENST00000617928.5 NP_055423.1 Q7L576-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CYFIP1ENST00000617928.5 linkuse as main transcriptc.666+34G>A intron_variant 1 NM_014608.6 ENSP00000481038.1 Q7L576-1
CYFIP1ENST00000610365.4 linkuse as main transcriptc.666+34G>A intron_variant 1 ENSP00000478779.1 Q7L576-1
CYFIP1ENST00000612288.2 linkuse as main transcriptc.666+34G>A intron_variant 3 ENSP00000479802.2 A0A087WVZ5

Frequencies

GnomAD3 genomes
AF:
0.235
AC:
35718
AN:
151722
Hom.:
4755
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.111
Gnomad AMI
AF:
0.336
Gnomad AMR
AF:
0.323
Gnomad ASJ
AF:
0.227
Gnomad EAS
AF:
0.293
Gnomad SAS
AF:
0.149
Gnomad FIN
AF:
0.266
Gnomad MID
AF:
0.339
Gnomad NFE
AF:
0.286
Gnomad OTH
AF:
0.274
GnomAD3 exomes
AF:
0.279
AC:
70167
AN:
251400
Hom.:
10807
AF XY:
0.271
AC XY:
36841
AN XY:
135880
show subpopulations
Gnomad AFR exome
AF:
0.106
Gnomad AMR exome
AF:
0.421
Gnomad ASJ exome
AF:
0.218
Gnomad EAS exome
AF:
0.303
Gnomad SAS exome
AF:
0.160
Gnomad FIN exome
AF:
0.272
Gnomad NFE exome
AF:
0.295
Gnomad OTH exome
AF:
0.289
GnomAD4 exome
AF:
0.279
AC:
407647
AN:
1461688
Hom.:
58887
Cov.:
38
AF XY:
0.276
AC XY:
200592
AN XY:
727118
show subpopulations
Gnomad4 AFR exome
AF:
0.108
Gnomad4 AMR exome
AF:
0.408
Gnomad4 ASJ exome
AF:
0.221
Gnomad4 EAS exome
AF:
0.265
Gnomad4 SAS exome
AF:
0.161
Gnomad4 FIN exome
AF:
0.270
Gnomad4 NFE exome
AF:
0.291
Gnomad4 OTH exome
AF:
0.264
GnomAD4 genome
AF:
0.235
AC:
35741
AN:
151840
Hom.:
4764
Cov.:
30
AF XY:
0.235
AC XY:
17412
AN XY:
74194
show subpopulations
Gnomad4 AFR
AF:
0.111
Gnomad4 AMR
AF:
0.323
Gnomad4 ASJ
AF:
0.227
Gnomad4 EAS
AF:
0.294
Gnomad4 SAS
AF:
0.148
Gnomad4 FIN
AF:
0.266
Gnomad4 NFE
AF:
0.286
Gnomad4 OTH
AF:
0.275
Alfa
AF:
0.258
Hom.:
1173
Bravo
AF:
0.242
Asia WGS
AF:
0.205
AC:
711
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
1.1
DANN
Benign
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: rs1109036; hg19: chr15-22933691; API