Variant chr15-22874598-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PP3_ModerateBP6_Very_StrongBP7BS2

The NM_014608.6(CYFIP1):c.3162C>T(p.Tyr1054=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00828 in 1,606,456 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0086 ( 91 hom. )

Consequence

CYFIP1
NM_014608.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.216

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]

CYFIP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PP3

BayesDel_noAF computational evidence supports a deleterious effect, 0.5

BP6

Variant 15-22874598-G-A is Benign according to our data. Variant chr15-22874598-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 783051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.216 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYFIP1	NM_014608.6 linkuse as main transcript	c.3162C>T	p.Tyr1054=	synonymous_variant	28/31	ENST00000617928.5	NP_055423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYFIP1	ENST00000617928.5 linkuse as main transcript	c.3162C>T	p.Tyr1054=	synonymous_variant	28/31	1	NM_014608.6	ENSP00000481038	P1	Q7L576-1

Frequencies

GnomAD3 genomes

AF:

0.00530

AC:

806

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00351

Gnomad FIN

AF:

0.00189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00955

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00531

AC:

1286

AN:

242018

Hom.:

AF XY:

0.00533

AC XY:

700

AN XY:

131352

show subpopulations

Gnomad AFR exome

AF:

0.00196

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.000407

Gnomad EAS exome

AF:

0.000567

Gnomad SAS exome

AF:

0.00499

Gnomad FIN exome

AF:

0.00274

Gnomad NFE exome

AF:

0.00881

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00859

AC:

12497

AN:

1454122

Hom.:

Cov.:

AF XY:

0.00837

AC XY:

6056

AN XY:

723428

show subpopulations

Gnomad4 AFR exome

AF:

0.00151

Gnomad4 AMR exome

AF:

0.00144

Gnomad4 ASJ exome

AF:

0.000810

Gnomad4 EAS exome

AF:

0.000128

Gnomad4 SAS exome

AF:

0.00549

Gnomad4 FIN exome

AF:

0.00311

Gnomad4 NFE exome

AF:

0.0102

Gnomad4 OTH exome

AF:

0.00725

GnomAD4 genome

AF:

0.00529

AC:

806

AN:

152334

Hom.:

Cov.:

AF XY:

0.00487

AC XY:

363

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.00189

Gnomad4 NFE

AF:

0.00955

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00810

Hom.:

Bravo

AF:

0.00467

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	CYFIP1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Pathogenic

0.50

CADD

Benign

0.85

DANN

Benign

0.20

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over