Genetic Variant CYFIP1:c.1234-17T>G (chr15-22926124-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_014608.6(CYFIP1):c.1234-17T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0264 in 1,613,878 control chromosomes in the GnomAD database, including 1,873 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.064 ( 659 hom., cov: 33)

Exomes 𝑓: 0.022 ( 1214 hom. )

Consequence

CYFIP1
NM_014608.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.114

Publications

8 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:

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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=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014608.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CYFIP1	NM_014608.6	MANE Select	c.1234-17T>G	intron	N/A	NP_055423.1	Q7L576-1
CYFIP1	NM_001324119.2		c.1336-17T>G	intron	N/A	NP_001311048.1
CYFIP1	NM_001287810.4		c.1234-17T>G	intron	N/A	NP_001274739.1	Q7L576-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CYFIP1	ENST00000617928.5	TSL:1 MANE Select	c.1234-17T>G	intron	N/A	ENSP00000481038.1	Q7L576-1
CYFIP1	ENST00000610365.4	TSL:1	c.1234-17T>G	intron	N/A	ENSP00000478779.1	Q7L576-1
CYFIP1	ENST00000900867.1		c.1279-17T>G	intron	N/A	ENSP00000570926.1

Frequencies

GnomAD3 genomes

AF:

0.0642

AC:

9766

AN:

152026

Hom.:

659

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0869

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.0822

Gnomad SAS

AF:

0.0699

Gnomad FIN

AF:

0.00631

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0113

Gnomad OTH

AF:

0.0531

GnomAD2 exomes

AF:

0.0450

AC:

11295

AN:

251216

AF XY:

0.0416

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.0917

Gnomad ASJ exome

AF:

0.0140

Gnomad EAS exome

AF:

0.0838

Gnomad FIN exome

AF:

0.00754

Gnomad NFE exome

AF:

0.0117

Gnomad OTH exome

AF:

0.0307

GnomAD4 exome

AF:

0.0225

AC:

32878

AN:

1461734

Hom.:

1214

Cov.:

AF XY:

0.0231

AC XY:

16797

AN XY:

727166

show subpopulations

African (AFR)

AF:

0.168

AC:

5639

AN:

33470

American (AMR)

AF:

0.0922

AC:

4122

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0146

AC:

382

AN:

26134

East Asian (EAS)

AF:

0.0842

AC:

3342

AN:

39698

South Asian (SAS)

AF:

0.0641

AC:

5528

AN:

86246

European-Finnish (FIN)

AF:

0.00948

AC:

506

AN:

53372

Middle Eastern (MID)

AF:

0.0212

AC:

122

AN:

5768

European-Non Finnish (NFE)

AF:

0.0102

AC:

11326

AN:

1111942

Other (OTH)

AF:

0.0316

AC:

1911

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

1559

3118

4677

6236

7795

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

644

1288

1932

2576

3220

<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:

0.0642

AC:

9774

AN:

152144

Hom.:

659

Cov.:

AF XY:

0.0644

AC XY:

4793

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.161

AC:

6679

AN:

41484

American (AMR)

AF:

0.0868

AC:

1327

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0141

AC:

AN:

3472

East Asian (EAS)

AF:

0.0820

AC:

424

AN:

5172

South Asian (SAS)

AF:

0.0697

AC:

336

AN:

4818

European-Finnish (FIN)

AF:

0.00631

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0113

AC:

767

AN:

67986

Other (OTH)

AF:

0.0525

AC:

111

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

432

865

1297

1730

2162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<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:

0.0316

Hom.:

424

Bravo

AF:

0.0732

Asia WGS

AF:

0.0960

AC:

335

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.87

(source)

DANN

Benign

0.67

PhyloP100

-0.11

PromoterAI

-0.0042

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over