Genetic Variant CDC42BPA:c.2905-7474T>A (chr1-227059459-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001394014.1(CDC42BPA):c.2905-7474T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0754 in 1,476,646 control chromosomes in the GnomAD database, including 4,888 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 0.063 ( 401 hom., cov: 32)

Exomes 𝑓: 0.077 ( 4487 hom. )

Consequence

CDC42BPA
NM_001394014.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.606

Publications

3 publications found

Variant links:

Genes affected

CDC42BPA (HGNC:1737): (CDC42 binding protein kinase alpha) The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase contains multiple functional domains. Its kinase domain is highly similar to that of the myotonic dystrophy protein kinase (DMPK). This kinase also contains a Rac interactive binding (CRIB) domain, and has been shown to bind CDC42. It may function as a CDC42 downstream effector mediating CDC42 induced peripheral actin formation, and promoting cytoskeletal reorganization. Multiple alternatively spliced transcript variants have been described. [provided by RefSeq, Sep 2018]

CDC42BPA links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001394014.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.64).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394014.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CDC42BPA	NM_001394014.1	MANE Select	c.2905-7474T>A	intron	N/A	NP_001380943.1	Q5VT25-2
CDC42BPA	NM_001387550.1		c.2953-48T>A	intron	N/A	NP_001374479.1	A0A0A0MRJ1
CDC42BPA	NM_001366019.2		c.2905-48T>A	intron	N/A	NP_001352948.1	Q5VT25-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CDC42BPA	ENST00000366766.8	TSL:5 MANE Select	c.2905-7474T>A	intron	N/A	ENSP00000355728.5	Q5VT25-2
CDC42BPA	ENST00000366769.7	TSL:1	c.2904+10318T>A	intron	N/A	ENSP00000355731.3	Q5VT25-5
CDC42BPA	ENST00000366764.8	TSL:1	c.2828-70T>A	intron	N/A	ENSP00000355726.5	A0A0A0MRJ0

Frequencies

GnomAD3 genomes

AF:

0.0634

AC:

9656

AN:

152210

Hom.:

397

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0173

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0895

Gnomad ASJ

AF:

0.0761

Gnomad EAS

AF:

0.155

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.0601

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0753

Gnomad OTH

AF:

0.0756

GnomAD2 exomes

AF:

0.0826

AC:

12616

AN:

152804

AF XY:

0.0849

show subpopulations

Gnomad AFR exome

AF:

0.0155

Gnomad AMR exome

AF:

0.0799

Gnomad ASJ exome

AF:

0.0851

Gnomad EAS exome

AF:

0.142

Gnomad FIN exome

AF:

0.0656

Gnomad NFE exome

AF:

0.0761

Gnomad OTH exome

AF:

0.0803

GnomAD4 exome

AF:

0.0768

AC:

101749

AN:

1324318

Hom.:

4487

Cov.:

AF XY:

0.0780

AC XY:

51315

AN XY:

657486

show subpopulations

African (AFR)

AF:

0.0166

AC:

501

AN:

30140

American (AMR)

AF:

0.0764

AC:

2723

AN:

35622

Ashkenazi Jewish (ASJ)

AF:

0.0843

AC:

2083

AN:

24702

East Asian (EAS)

AF:

0.151

AC:

5353

AN:

35490

South Asian (SAS)

AF:

0.105

AC:

8164

AN:

77710

European-Finnish (FIN)

AF:

0.0655

AC:

3164

AN:

48308

Middle Eastern (MID)

AF:

0.120

AC:

667

AN:

5558

European-Non Finnish (NFE)

AF:

0.0740

AC:

74793

AN:

1011042

Other (OTH)

AF:

0.0772

AC:

4301

AN:

55746

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

4535

9070

13605

18140

22675

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2760

5520

8280

11040

13800

<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:

0.0634

AC:

9663

AN:

152328

Hom.:

401

Cov.:

AF XY:

0.0648

AC XY:

4825

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0172

AC:

717

AN:

41586

American (AMR)

AF:

0.0893

AC:

1366

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0761

AC:

264

AN:

3470

East Asian (EAS)

AF:

0.154

AC:

797

AN:

5180

South Asian (SAS)

AF:

0.111

AC:

537

AN:

4830

European-Finnish (FIN)

AF:

0.0601

AC:

638

AN:

10622

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0753

AC:

5123

AN:

68022

Other (OTH)

AF:

0.0833

AC:

176

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

471

942

1414

1885

2356

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<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:

0.0401

Hom.:

Bravo

AF:

0.0594

Asia WGS

AF:

0.140

AC:

490

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

7.2

(source)

DANN

Benign

0.80

PhyloP100

0.61

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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