rs12740705

Positions:

• chr1-22094620-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001791.4(CDC42):​c.*3103C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 151,790 control chromosomes in the GnomAD database, including 1,304 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 0.12 (1304 hom., cov: 31)
• Consequence: CDC42 NM_001791.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.678

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC42	NM_001791.4	c.*3103C>T		3_prime_UTR_variant	6/6	ENST00000656825.1	NP_001782.1
CDC42	NM_001039802.2	c.*3103C>T		3_prime_UTR_variant	7/7		NP_001034891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC42	ENST00000656825.1	c.*3103C>T		3_prime_UTR_variant	6/6		NM_001791.4	ENSP00000499457	P3

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18893 AN: 151672 Hom.: 1304 Cov.: 31

Gnomad AFR AF: 0.0806

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0688

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.125 AC: 18899 AN: 151790 Hom.: 1304 Cov.: 31 AF XY: 0.124 AC XY: 9237 AN XY: 74202

Gnomad4 AFR AF: 0.0806

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.0693

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.136

Alfa AF: 0.131 Hom.: 680

Bravo AF: 0.126

Asia WGS AF: 0.0940 AC: 329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12740705; hg19: chr1-22421113;