1-22081972-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001791.4(CDC42):c.178+178C>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 152,252 control chromosomes in the GnomAD database, including 68,221 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.95 (68221 hom., cov: 32)
• Consequence: CDC42 NM_001791.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0910

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-22081972-C-T is Benign according to our data. Variant chr1-22081972-C-T is described in ClinVar as [Benign]. Clinvar id is 1289394.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC42	NM_001791.4	c.178+178C>T		intron_variant		ENST00000656825.1
CDC42	NM_001039802.2	c.178+178C>T		intron_variant
CDC42	NM_044472.3	c.178+178C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC42	ENST00000656825.1	c.178+178C>T		intron_variant			NM_001791.4	P3

Frequencies

GnomAD3 genomes AF: 0.946 AC: 143913 AN: 152134 Hom.: 68161 Cov.: 32

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: 0.946

Gnomad FIN AF: 0.889

Gnomad MID AF: 0.899

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: 144032 AN: 152252 Hom.: 68221 Cov.: 32 AF XY: 0.946 AC XY: 70377 AN XY: 74428

Gnomad4 AFR AF: 0.989

Gnomad4 AMR AF: 0.953

Gnomad4 ASJ AF: 0.930

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.946

Gnomad4 FIN AF: 0.889

Gnomad4 NFE AF: 0.925

Gnomad4 OTH AF: 0.955

Alfa AF: 0.932 Hom.: 10161

Bravo AF: 0.953

Asia WGS AF: 0.981 AC: 3411 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.2
Dann	Benign	0.52

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

Other links and lift over

dbSNP: rs2056976; hg19: chr1-22408465;