dbSNP rs728693: CYFIP2:c.3039+3682G>A (chr5-157365280-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001037333.3(CYFIP2):c.3039+3682G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 152,016 control chromosomes in the GnomAD database, including 22,425 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 0.53 ( 22425 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

CYFIP2
NM_001037333.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.702

Publications

6 publications found

Variant links:

Genes affected

CYFIP2 (HGNC:13760): (cytoplasmic FMR1 interacting protein 2) Predicted to enable small GTPase binding activity. Involved in activation of cysteine-type endopeptidase activity; apoptotic process; and cell-cell adhesion. Located in perinuclear region of cytoplasm and synapse. Part of SCAR complex. Implicated in developmental and epileptic encephalopathy 65. [provided by Alliance of Genome Resources, Apr 2022]

CYFIP2 links:

ENSG00000285868 (HGNC:):

ENSG00000285868 links:

NIPAL4-DT (HGNC:55542): (NIPAL4 divergent transcript)

NIPAL4-DT 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=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037333.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CYFIP2	NM_001037333.3	MANE Select	c.3039+3682G>A	intron	N/A	NP_001032410.1
CYFIP2	NM_001291722.2		c.3114+3682G>A	intron	N/A	NP_001278651.1
CYFIP2	NM_014376.4		c.3039+3682G>A	intron	N/A	NP_055191.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CYFIP2	ENST00000620254.5	TSL:1 MANE Select	c.3039+3682G>A	intron	N/A	ENSP00000479968.1
CYFIP2	ENST00000616178.4	TSL:1	c.3114+3682G>A	intron	N/A	ENSP00000479719.1
CYFIP2	ENST00000618329.4	TSL:1	c.3039+3682G>A	intron	N/A	ENSP00000484819.1

Frequencies

GnomAD3 genomes

AF:

0.532

AC:

80878

AN:

151898

Hom.:

22412

Cov.:

show subpopulations

Gnomad AFR

AF:

0.627

Gnomad AMI

AF:

0.558

Gnomad AMR

AF:

0.438

Gnomad ASJ

AF:

0.564

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.316

Gnomad FIN

AF:

0.461

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.552

Gnomad OTH

AF:

0.533

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.532

AC:

80944

AN:

152016

Hom.:

22425

Cov.:

AF XY:

0.518

AC XY:

38481

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.627

AC:

25980

AN:

41450

American (AMR)

AF:

0.438

AC:

6693

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.564

AC:

1957

AN:

3468

East Asian (EAS)

AF:

0.125

AC:

649

AN:

5184

South Asian (SAS)

AF:

0.317

AC:

1529

AN:

4826

European-Finnish (FIN)

AF:

0.461

AC:

4858

AN:

10538

Middle Eastern (MID)

AF:

0.527

AC:

155

AN:

294

European-Non Finnish (NFE)

AF:

0.552

AC:

37498

AN:

67958

Other (OTH)

AF:

0.530

AC:

1117

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1898

3796

5693

7591

9489

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

684

1368

2052

2736

3420

<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:

0.544

Hom.:

13331

Bravo

AF:

0.538

Asia WGS

AF:

0.255

AC:

888

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

4.1

(source)

DANN

Benign

0.38

PhyloP100

0.70

Mutation Taster

=100/0

polymorphism (auto)

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over