Genetic Variant CDC42:c.-51+10092G>T (chr1-22062834-G-T) – 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.-51+10092G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.946 in 151,566 control chromosomes in the GnomAD database, including 67,950 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 0.95 ( 67950 hom., cov: 27)

Consequence

CDC42
NM_001791.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0200

Publications

5 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:

CDC42-IT1 (HGNC:41317): (CDC42 intronic transcript 1)

CDC42-IT1 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=-1.0).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CDC42	NM_001791.4 link	c.-51+10092G>T	intron_variant	Intron 1 of 5	ENST00000656825.1	NP_001782.1	P60953-2A0A024RAA5
CDC42	NM_001039802.2 link	c.-177+10092G>T	intron_variant	Intron 1 of 6		NP_001034891.1	P60953-2A0A024RAA5
CDC42	NM_044472.3 link	c.-51+10092G>T	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.-51+10092G>T		intron_variant	Intron 1 of 5		NM_001791.4	ENSP00000499457.1		P60953-2
ENSG00000289694	ENST00000695856.1 link	c.-50-15595G>T		intron_variant	Intron 1 of 5			ENSP00000512221.1

Frequencies

GnomAD3 genomes

AF:

0.946

AC:

143335

AN:

151448

Hom.:

67890

Cov.:

show subpopulations

Gnomad AFR

AF:

0.989

Gnomad AMI

AF:

0.859

Gnomad AMR

AF:

0.953

Gnomad ASJ

AF:

0.930

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.947

Gnomad FIN

AF:

0.894

Gnomad MID

AF:

0.910

Gnomad NFE

AF:

0.925

Gnomad OTH

AF:

0.955

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

GnomAD4 genome

AF:

0.946

AC:

143454

AN:

151566

Hom.:

67950

Cov.:

AF XY:

0.946

AC XY:

70011

AN XY:

73976

show subpopulations

African (AFR)

AF:

0.989

AC:

40858

AN:

41328

American (AMR)

AF:

0.954

AC:

14469

AN:

15174

Ashkenazi Jewish (ASJ)

AF:

0.930

AC:

3225

AN:

3468

East Asian (EAS)

AF:

0.999

AC:

5173

AN:

5176

South Asian (SAS)

AF:

0.947

AC:

4546

AN:

4802

European-Finnish (FIN)

AF:

0.894

AC:

9256

AN:

10358

Middle Eastern (MID)

AF:

0.910

AC:

262

AN:

288

European-Non Finnish (NFE)

AF:

0.925

AC:

62879

AN:

67964

Other (OTH)

AF:

0.955

AC:

2004

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

Heterozygous variant carriers

380

761

1141

1522

1902

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<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:

0.933

Hom.:

76686

Bravo

AF:

0.953

Asia WGS

AF:

0.981

AC:

3411

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.9

(source)

DANN

Benign

0.74

PhyloP100

-0.020

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