rs17837976

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001791.4(CDC42):c.106-3T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00585 in 1,607,138 control chromosomes in the GnomAD database, including 304 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 44 hom., cov: 33)

Exomes 𝑓: 0.0055 ( 260 hom. )

Consequence

CDC42
NM_001791.4 splice_region, intron

Scores

Splicing: ADA: 0.001283

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.720

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 1-22081719-T-C is Benign according to our data. Variant chr1-22081719-T-C is described in ClinVar as [Benign]. Clinvar id is 1167405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-22081719-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CDC42	NM_001791.4 link	c.106-3T>C	splice_region_variant, intron_variant	Intron 2 of 5	ENST00000656825.1	NP_001782.1	P60953-2A0A024RAA5
CDC42	NM_001039802.2 link	c.106-3T>C	splice_region_variant, intron_variant	Intron 3 of 6		NP_001034891.1	P60953-2A0A024RAA5
CDC42	NM_044472.3 link	c.106-3T>C	splice_region_variant, intron_variant	Intron 2 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.106-3T>C		splice_region_variant, intron_variant	Intron 2 of 5		NM_001791.4	ENSP00000499457.1		P60953-2
ENSG00000289694	ENST00000695855.1 link	c.106-3T>C		splice_region_variant, intron_variant	Intron 2 of 5			ENSP00000512220.1

Frequencies

GnomAD3 genomes

AF:

0.00878

AC:

1336

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00215

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0594

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00451

Gnomad OTH

AF:

0.00718

GnomAD2 exomes

AF:

0.0155

AC:

3884

AN:

250174

AF XY:

0.0122

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.0982

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00125

Gnomad NFE exome

AF:

0.00326

Gnomad OTH exome

AF:

0.00986

GnomAD4 exome

AF:

0.00554

AC:

8056

AN:

1454776

Hom.:

260

Cov.:

AF XY:

0.00512

AC XY:

3709

AN XY:

724252

show subpopulations

African (AFR)

AF:

0.00114

AC:

AN:

33306

American (AMR)

AF:

0.0931

AC:

4146

AN:

44524

Ashkenazi Jewish (ASJ)

AF:

0.00177

AC:

AN:

26052

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.000221

AC:

AN:

85980

European-Finnish (FIN)

AF:

0.00130

AC:

AN:

53230

Middle Eastern (MID)

AF:

0.000523

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00311

AC:

3436

AN:

1106174

Other (OTH)

AF:

0.00497

AC:

299

AN:

60108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

347

694

1042

1389

1736

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00880

AC:

1341

AN:

152362

Hom.:

Cov.:

AF XY:

0.00927

AC XY:

691

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.00214

AC:

AN:

41596

American (AMR)

AF:

0.0596

AC:

912

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00451

AC:

307

AN:

68034

Other (OTH)

AF:

0.00710

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

122

184

245

306

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00942

Hom.:

Bravo

AF:

0.0124

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.00360

EpiControl

AF:

0.00207

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 05, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0013

dbscSNV1_RF

Benign

0.024

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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rs17837976

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over