15-22873574-G-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP6_Moderate BP7

The NM_014608.6(CYFIP1):c.3366C>T(p.Asp1122=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000214 in 1,614,220 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: CYFIP1 NM_014608.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.411

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]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 15-22873574-G-A is Benign according to our data. Variant chr15-22873574-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 750193.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.411 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYFIP1	NM_014608.6	c.3366C>T	p.Asp1122=	synonymous_variant	29/31	ENST00000617928.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYFIP1	ENST00000617928.5	c.3366C>T	p.Asp1122=	synonymous_variant	29/31	1	NM_014608.6	P1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152220 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000915 AC: 23 AN: 251390 Hom.: 0 AF XY: 0.000103 AC XY: 14 AN XY: 135870

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000231 AC: 337 AN: 1461882 Hom.: 0 Cov.: 32 AF XY: 0.000219 AC XY: 159 AN XY: 727240

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000291

Gnomad4 OTH exome AF: 0.000132

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152338 Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2 AN XY: 74492

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000134 Hom.: 0

Bravo AF: 0.0000831

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	0.0
Cadd	Benign	4.1
Dann	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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

Other links and lift over

dbSNP: rs140215868; hg19: chr15-22999494; COSMIC: COSV57416684; COSMIC: COSV57416684;