Genetic Variant CYFIP1:n.140A>G (chr15-22914964-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000619290.4(CYFIP1):n.140A>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 0.367 in 1,426,870 control chromosomes in the GnomAD database, including 99,406 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 0.43 ( 15089 hom., cov: 31)

Exomes 𝑓: 0.36 ( 84317 hom. )

Consequence

CYFIP1
ENST00000619290.4 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.89

Publications

6 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=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYFIP1	NM_014608.6 link	c.1829-82A>G		intron_variant	Intron 16 of 30	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.1829-82A>G		intron_variant	Intron 16 of 30	1	NM_014608.6	ENSP00000481038.1		Q7L576-1

Frequencies

GnomAD3 genomes

AF:

0.432

AC:

65398

AN:

151554

Hom.:

15049

Cov.:

show subpopulations

Gnomad AFR

AF:

0.585

Gnomad AMI

AF:

0.444

Gnomad AMR

AF:

0.474

Gnomad ASJ

AF:

0.397

Gnomad EAS

AF:

0.479

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.340

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.349

Gnomad OTH

AF:

0.389

GnomAD4 exome

AF:

0.359

AC:

457488

AN:

1275202

Hom.:

84317

Cov.:

AF XY:

0.357

AC XY:

223893

AN XY:

626624

show subpopulations

African (AFR)

AF:

0.590

AC:

16845

AN:

28542

American (AMR)

AF:

0.532

AC:

14313

AN:

26888

Ashkenazi Jewish (ASJ)

AF:

0.396

AC:

7776

AN:

19660

East Asian (EAS)

AF:

0.498

AC:

18027

AN:

36172

South Asian (SAS)

AF:

0.356

AC:

23202

AN:

65120

European-Finnish (FIN)

AF:

0.343

AC:

15381

AN:

44902

Middle Eastern (MID)

AF:

0.360

AC:

1702

AN:

4722

European-Non Finnish (NFE)

AF:

0.342

AC:

340540

AN:

995888

Other (OTH)

AF:

0.370

AC:

19702

AN:

53308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

13534

27069

40603

54138

67672

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11424

22848

34272

45696

57120

<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:

0.432

AC:

65488

AN:

151668

Hom.:

15089

Cov.:

AF XY:

0.431

AC XY:

31904

AN XY:

74076

show subpopulations

African (AFR)

AF:

0.585

AC:

24172

AN:

41354

American (AMR)

AF:

0.475

AC:

7239

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.397

AC:

1377

AN:

3470

East Asian (EAS)

AF:

0.480

AC:

2472

AN:

5152

South Asian (SAS)

AF:

0.354

AC:

1702

AN:

4808

European-Finnish (FIN)

AF:

0.340

AC:

3555

AN:

10462

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.348

AC:

23654

AN:

67874

Other (OTH)

AF:

0.388

AC:

816

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1779

3557

5336

7114

8893

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

598

1196

1794

2392

2990

<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:

0.372

Hom.:

44966

Bravo

AF:

0.449

Asia WGS

AF:

0.402

AC:

1399

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.044

(source)

DANN

Benign

0.31

PhyloP100

-1.9

Splicing

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