Genetic Variant CDC42EP4:c.*217T>C (chr17-73285213-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_012121.5(CDC42EP4):c.*217T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 439,882 control chromosomes in the GnomAD database, including 67,365 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 0.55 ( 22755 hom., cov: 33)

Exomes 𝑓: 0.55 ( 44610 hom. )

Consequence

CDC42EP4
NM_012121.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.754

Publications

9 publications found

Variant links:

Genes affected

CDC42EP4 (HGNC:17147): (CDC42 effector protein 4) The product of this gene is a member of the CDC42-binding protein family. Members of this family interact with Rho family GTPases and regulate the organization of the actin cytoskeleton. This protein has been shown to bind both CDC42 and TC10 GTPases in a GTP-dependent manner. When overexpressed in fibroblasts, this protein was able to induce pseudopodia formation, which suggested a role in inducing actin filament assembly and cell shape control. [provided by RefSeq, Jul 2008]

CDC42EP4 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC42EP4	NM_012121.5 link	c.*217T>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000335793.4	NP_036253.2	Q9H3Q1-1B2R6D8
CDC42EP4	XM_005257182.3 link	c.*217T>C		3_prime_UTR_variant	Exon 2 of 2		XP_005257239.1	Q9H3Q1-1B2R6D8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CDC42EP4	ENST00000335793.4 link	c.*217T>C	3_prime_UTR_variant	Exon 2 of 2	1	NM_012121.5	ENSP00000338258.3	Q9H3Q1-1
CDC42EP4	ENST00000439510.2 link	c.*217T>C	3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000404270.2	Q9H3Q1-2
CDC42EP4	ENST00000581014.1 link	c.*245T>C	3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000464104.1	J3QR93
CDC42EP4	ENST00000630622.1 link	c.*245T>C	downstream_gene_variant		5		ENSP00000485861.1	J3QR93

Frequencies

GnomAD3 genomes

AF:

0.547

AC:

83108

AN:

151944

Hom.:

22738

Cov.:

show subpopulations

Gnomad AFR

AF:

0.503

Gnomad AMI

AF:

0.585

Gnomad AMR

AF:

0.577

Gnomad ASJ

AF:

0.535

Gnomad EAS

AF:

0.610

Gnomad SAS

AF:

0.610

Gnomad FIN

AF:

0.618

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.547

Gnomad OTH

AF:

0.533

GnomAD4 exome

AF:

0.552

AC:

159019

AN:

287820

Hom.:

44610

Cov.:

AF XY:

0.553

AC XY:

81452

AN XY:

147176

show subpopulations

African (AFR)

AF:

0.498

AC:

4508

AN:

9060

American (AMR)

AF:

0.570

AC:

6554

AN:

11494

Ashkenazi Jewish (ASJ)

AF:

0.532

AC:

5325

AN:

10010

East Asian (EAS)

AF:

0.590

AC:

14502

AN:

24570

South Asian (SAS)

AF:

0.598

AC:

7624

AN:

12746

European-Finnish (FIN)

AF:

0.601

AC:

12737

AN:

21182

Middle Eastern (MID)

AF:

0.515

AC:

743

AN:

1444

European-Non Finnish (NFE)

AF:

0.542

AC:

97103

AN:

179166

Other (OTH)

AF:

0.547

AC:

9923

AN:

18148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

3257

6513

9770

13026

16283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.547

AC:

83165

AN:

152062

Hom.:

22755

Cov.:

AF XY:

0.554

AC XY:

41203

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.503

AC:

20883

AN:

41490

American (AMR)

AF:

0.578

AC:

8830

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.535

AC:

1857

AN:

3472

East Asian (EAS)

AF:

0.610

AC:

3141

AN:

5148

South Asian (SAS)

AF:

0.610

AC:

2939

AN:

4818

European-Finnish (FIN)

AF:

0.618

AC:

6539

AN:

10584

Middle Eastern (MID)

AF:

0.473

AC:

139

AN:

294

European-Non Finnish (NFE)

AF:

0.547

AC:

37185

AN:

67946

Other (OTH)

AF:

0.530

AC:

1121

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1975

3950

5925

7900

9875

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.539

Hom.:

45778

Bravo

AF:

0.537

Asia WGS

AF:

0.603

AC:

2101

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.28

(source)

DANN

Benign

0.25

PhyloP100

-0.75

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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17-73285213-A-G

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