Variant chr1-22081707-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001791.4(CDC42):c.106-15T>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000402 in 1,560,858 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00043 ( 1 hom. )

Consequence

CDC42
NM_001791.4 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.88

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 1-22081707-T-A is Benign according to our data. Variant chr1-22081707-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1641124.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CDC42	NM_001791.4 linkuse as main transcript	c.106-15T>A	splice_polypyrimidine_tract_variant, intron_variant	ENST00000656825.1
CDC42	NM_001039802.2 linkuse as main transcript	c.106-15T>A	splice_polypyrimidine_tract_variant, intron_variant
CDC42	NM_044472.3 linkuse as main transcript	c.106-15T>A	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.106-15T>A		splice_polypyrimidine_tract_variant, intron_variant			NM_001791.4	P3	P60953-2

Frequencies

GnomAD3 genomes

AF:

0.000127

AC:

AN:

150002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000663

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000270

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000268

AC:

AN:

245856

Hom.:

AF XY:

0.000241

AC XY:

AN XY:

132916

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.000402

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000100

Gnomad FIN exome

AF:

0.0000961

Gnomad NFE exome

AF:

0.000434

Gnomad OTH exome

AF:

0.000335

GnomAD4 exome

AF:

0.000432

AC:

609

AN:

1410738

Hom.:

Cov.:

AF XY:

0.000429

AC XY:

302

AN XY:

704530

show subpopulations

Gnomad4 AFR exome

AF:

0.000124

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.000272

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000588

Gnomad4 FIN exome

AF:

0.0000567

Gnomad4 NFE exome

AF:

0.000518

Gnomad4 OTH exome

AF:

0.000528

GnomAD4 genome

AF:

0.000127

AC:

AN:

150120

Hom.:

Cov.:

AF XY:

0.0000818

AC XY:

AN XY:

73372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000662

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000270

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000385

Hom.:

Bravo

AF:

0.000181

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 21, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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