Variant 1-22078709-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001791.4(CDC42):c.105+126T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,509,282 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0077 ( 14 hom., cov: 32)

Exomes 𝑓: 0.011 ( 88 hom. )

Consequence

CDC42
NM_001791.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.22

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.23).

BP6

Variant 1-22078709-T-A is Benign according to our data. Variant chr1-22078709-T-A is described in ClinVar as [Benign]. Clinvar id is 1694498.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 1174 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CDC42	NM_001791.4 linkuse as main transcript	c.105+126T>A	intron_variant	ENST00000656825.1	NP_001782.1
CDC42	NM_001039802.2 linkuse as main transcript	c.105+126T>A	intron_variant		NP_001034891.1
CDC42	NM_044472.3 linkuse as main transcript	c.105+126T>A	intron_variant		NP_426359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC42	ENST00000656825.1 linkuse as main transcript	c.105+126T>A		intron_variant			NM_001791.4	ENSP00000499457	P3	P60953-2

Frequencies

GnomAD3 genomes

AF:

0.00772

AC:

1175

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0193

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0123

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00698

AC:

942

AN:

135030

Hom.:

AF XY:

0.00675

AC XY:

488

AN XY:

72286

show subpopulations

Gnomad AFR exome

AF:

0.00170

Gnomad AMR exome

AF:

0.00223

Gnomad ASJ exome

AF:

0.00239

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000822

Gnomad FIN exome

AF:

0.0181

Gnomad NFE exome

AF:

0.0115

Gnomad OTH exome

AF:

0.00487

GnomAD4 exome

AF:

0.0110

AC:

14928

AN:

1356972

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

7053

AN XY:

668776

show subpopulations

Gnomad4 AFR exome

AF:

0.00160

Gnomad4 AMR exome

AF:

0.00196

Gnomad4 ASJ exome

AF:

0.00185

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000796

Gnomad4 FIN exome

AF:

0.0173

Gnomad4 NFE exome

AF:

0.0128

Gnomad4 OTH exome

AF:

0.00815

GnomAD4 genome

AF:

0.00771

AC:

1174

AN:

152310

Hom.:

Cov.:

AF XY:

0.00777

AC XY:

579

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00195

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0193

Gnomad4 NFE

AF:

0.0123

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00954

Hom.:

Bravo

AF:

0.00605

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

CDC42: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.98

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over