Genetic Variant CYFIP1:n.3332C>G (chr15-22869605-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000619348.4(CYFIP1):n.3332C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 154,020 control chromosomes in the GnomAD database, including 1,781 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 0.12 ( 1772 hom., cov: 33)

Exomes 𝑓: 0.057 ( 9 hom. )

Consequence

CYFIP1
ENST00000619348.4 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.631

Publications

4 publications found

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:

NIPA2 (HGNC:17044): (NIPA magnesium transporter 2) This gene encodes a possible magnesium transporter. This gene is located adjacent to the imprinted domain in the Prader-Willi syndrome deletion region of chromosome 15. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 3, 7 and 21.[provided by RefSeq, May 2010]

NIPA2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYFIP1	NM_014608.6 link	c.*423C>G		3_prime_UTR_variant	Exon 31 of 31	ENST00000617928.5	NP_055423.1	Q7L576-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYFIP1	ENST00000617928.5 link	c.*423C>G		3_prime_UTR_variant	Exon 31 of 31	1	NM_014608.6	ENSP00000481038.1		Q7L576-1

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17795

AN:

152050

Hom.:

1763

Cov.:

show subpopulations

Gnomad AFR

AF:

0.256

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.0776

Gnomad ASJ

AF:

0.0726

Gnomad EAS

AF:

0.286

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.0280

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0432

Gnomad OTH

AF:

0.110

GnomAD4 exome

AF:

0.0567

AC:

105

AN:

1852

Hom.:

Cov.:

AF XY:

0.0754

AC XY:

AN XY:

942

show subpopulations

African (AFR)

AF:

0.267

AC:

AN:

American (AMR)

AF:

0.0294

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

AN:

East Asian (EAS)

AF:

0.271

AC:

AN:

South Asian (SAS)

AF:

0.0800

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0392

AC:

AN:

1404

Other (OTH)

AF:

0.0645

AC:

AN:

124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.117

AC:

17832

AN:

152168

Hom.:

1772

Cov.:

AF XY:

0.117

AC XY:

8718

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.256

AC:

10614

AN:

41496

American (AMR)

AF:

0.0774

AC:

1182

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0726

AC:

252

AN:

3472

East Asian (EAS)

AF:

0.285

AC:

1479

AN:

5182

South Asian (SAS)

AF:

0.143

AC:

691

AN:

4824

European-Finnish (FIN)

AF:

0.0280

AC:

297

AN:

10604

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0432

AC:

2939

AN:

68000

Other (OTH)

AF:

0.116

AC:

244

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

744

1488

2232

2976

3720

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0743

Hom.:

108

Bravo

AF:

0.126

Asia WGS

AF:

0.251

AC:

871

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

5.1

(source)

DANN

Benign

0.71

PhyloP100

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over