rs11800014

Variant names:

• chr1-22087577-C-T
• rs11800014
• NM_001791.4:c.486+711C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001791.4(CDC42):​c.486+711C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,014 control chromosomes in the GnomAD database, including 2,498 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 0.18 (2498 hom., cov: 32)
• Consequence: CDC42 NM_001791.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000289694 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC42	NM_001791.4	c.486+711C>T		intron_variant	Intron 5 of 5	ENST00000656825.1	NP_001782.1
CDC42	NM_001039802.2	c.486+711C>T		intron_variant	Intron 6 of 6		NP_001034891.1
CDC42	NM_044472.3	c.486+711C>T		intron_variant	Intron 5 of 5		NP_426359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC42	ENST00000656825.1	c.486+711C>T		intron_variant	Intron 5 of 5		NM_001791.4	ENSP00000499457.1
ENSG00000289694	ENST00000695856.1	c.486+711C>T		intron_variant	Intron 5 of 5			ENSP00000512221.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26647 AN: 151896 Hom.: 2480 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0626

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.176 AC: 26706 AN: 152014 Hom.: 2498 Cov.: 32 AF XY: 0.174 AC XY: 12930 AN XY: 74304

African (AFR) AF: 0.221 AC: 9143 AN: 41446

American (AMR) AF: 0.200 AC: 3058 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 539 AN: 3470

East Asian (EAS) AF: 0.121 AC: 627 AN: 5174

South Asian (SAS) AF: 0.0633 AC: 305 AN: 4820

European-Finnish (FIN) AF: 0.157 AC: 1657 AN: 10562

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.158 AC: 10734 AN: 67956

Other (OTH) AF: 0.178 AC: 375 AN: 2112

Alfa AF: 0.166 Hom.: 8250

Bravo AF: 0.183

Asia WGS AF: 0.107 AC: 375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.61
DANN	Benign	0.61
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11800014; hg19: chr1-22414070;