dbSNP rs17837965: CDC42:c.-50-10297A>G (chr1-22068132-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_001791.4(CDC42):c.-50-10297A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0555 in 152,250 control chromosomes in the GnomAD database, including 376 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 0.056 ( 376 hom., cov: 32)

Consequence

CDC42
NM_001791.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0740

Publications

10 publications found

Variant links:

Genes affected

CDC42 (HGNC:1736): (cell division cycle 42) The protein encoded by this gene is a small GTPase of the Rho-subfamily, which regulates signaling pathways that control diverse cellular functions including cell morphology, migration, endocytosis and cell cycle progression. This protein is highly similar to Saccharomyces cerevisiae Cdc 42, and is able to complement the yeast cdc42-1 mutant. The product of oncogene Dbl was reported to specifically catalyze the dissociation of GDP from this protein. This protein could regulate actin polymerization through its direct binding to Neural Wiskott-Aldrich syndrome protein (N-WASP), which subsequently activates Arp2/3 complex. Alternative splicing of this gene results in multiple transcript variants. Pseudogenes of this gene have been identified on chromosomes 3, 4, 5, 7, 8 and 20. [provided by RefSeq, Apr 2013]

CDC42 links:

ENSG00000289694 (HGNC:):

ENSG00000289694 links:

MPHOSPH6P1 (HGNC:54549): (MPHOSPH6 pseudogene 1)

MPHOSPH6P1 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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CDC42	NM_001791.4 link	c.-50-10297A>G	intron_variant	Intron 1 of 5	ENST00000656825.1	NP_001782.1	P60953-2A0A024RAA5
MPHOSPH6P1		n.22068132A>G	intragenic_variant
CDC42	NM_001039802.2 link	c.-176-5962A>G	intron_variant	Intron 1 of 6		NP_001034891.1	P60953-2A0A024RAA5
CDC42	NM_044472.3 link	c.-50-10297A>G	intron_variant	Intron 1 of 5		NP_426359.1	P60953-1A0A024RAA6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC42	ENST00000656825.1 link	c.-50-10297A>G		intron_variant	Intron 1 of 5		NM_001791.4	ENSP00000499457.1		P60953-2
ENSG00000289694	ENST00000695856.1 link	c.-50-10297A>G		intron_variant	Intron 1 of 5			ENSP00000512221.1

Frequencies

GnomAD3 genomes

AF:

0.0556

AC:

8459

AN:

152132

Hom.:

377

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0104

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.0922

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.0495

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0543

Gnomad OTH

AF:

0.0588

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0555

AC:

8453

AN:

152250

Hom.:

376

Cov.:

AF XY:

0.0592

AC XY:

4407

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0104

AC:

432

AN:

41570

American (AMR)

AF:

0.117

AC:

1782

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0922

AC:

320

AN:

3470

East Asian (EAS)

AF:

0.121

AC:

626

AN:

5178

South Asian (SAS)

AF:

0.0498

AC:

240

AN:

4822

European-Finnish (FIN)

AF:

0.103

AC:

1089

AN:

10608

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0543

AC:

3690

AN:

68008

Other (OTH)

AF:

0.0582

AC:

123

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

401

803

1204

1606

2007

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<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:

0.0600

Hom.:

223

Bravo

AF:

0.0549

Asia WGS

AF:

0.0790

AC:

277

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.4

(source)

DANN

Benign

0.84

PhyloP100

-0.074

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over