Variant chr1-22081719-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001791.4(CDC42):c.106-3T>C variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.001283

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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	MANE
CDC42	NM_001791.4 linkuse as main transcript	c.106-3T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000656825.1
CDC42	NM_001039802.2 linkuse as main transcript	c.106-3T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
CDC42	NM_044472.3 linkuse as main transcript	c.106-3T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC42	ENST00000656825.1 linkuse as main transcript	c.106-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_001791.4	P3	P60953-2

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

GnomAD3 exomes

AF:

0.0155

AC:

3884

AN:

250174

Hom.:

199

AF XY:

0.0122

AC XY:

1650

AN XY:

135212

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 SAS exome

AF:

0.000230

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

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.0931

Gnomad4 ASJ exome

AF:

0.00177

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000221

Gnomad4 FIN exome

AF:

0.00130

Gnomad4 NFE exome

AF:

0.00311

Gnomad4 OTH exome

AF:

0.00497

GnomAD4 genome

AF:

0.00880

AC:

1341

AN:

152362

Hom.:

Cov.:

AF XY:

0.00927

AC XY:

691

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00214

Gnomad4 AMR

AF:

0.0596

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00451

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00950

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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