1-22062834-G-T

Variant names:

• chr1-22062834-G-T
• rs2473323
• NM_001791.4:c.-51+10092G>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.-51+10092G>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 151,566 control chromosomes in the GnomAD database, including 67,950 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 0.95 (67950 hom., cov: 27)
• Consequence: CDC42 NM_001791.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0200
• Publications: 5 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]

ENSG00000289694 (HGNC:):

CDC42-IT1 (HGNC:41317): (CDC42 intronic transcript 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• 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 rank	MANE	Protein	UniProt
CDC42	NM_001791.4	c.-51+10092G>T		intron_variant	Intron 1 of 5	ENST00000656825.1	NP_001782.1
CDC42	NM_001039802.2	c.-177+10092G>T		intron_variant	Intron 1 of 6		NP_001034891.1
CDC42	NM_044472.3	c.-51+10092G>T		intron_variant	Intron 1 of 5		NP_426359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC42	ENST00000656825.1	c.-51+10092G>T		intron_variant	Intron 1 of 5		NM_001791.4	ENSP00000499457.1
ENSG00000289694	ENST00000695856.1	c.-50-15595G>T		intron_variant	Intron 1 of 5			ENSP00000512221.1

Frequencies

GnomAD3 genomes AF: 0.946 AC: 143335 AN: 151448 Hom.: 67890 Cov.: 27

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: 0.947

Gnomad FIN AF: 0.894

Gnomad MID AF: 0.910

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: 143454 AN: 151566 Hom.: 67950 Cov.: 27 AF XY: 0.946 AC XY: 70011 AN XY: 73976

African (AFR) AF: 0.989 AC: 40858 AN: 41328

American (AMR) AF: 0.954 AC: 14469 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.930 AC: 3225 AN: 3468

East Asian (EAS) AF: 0.999 AC: 5173 AN: 5176

South Asian (SAS) AF: 0.947 AC: 4546 AN: 4802

European-Finnish (FIN) AF: 0.894 AC: 9256 AN: 10358

Middle Eastern (MID) AF: 0.910 AC: 262 AN: 288

European-Non Finnish (NFE) AF: 0.925 AC: 62879 AN: 67964

Other (OTH) AF: 0.955 AC: 2004 AN: 2098

Alfa AF: 0.933 Hom.: 76686

Bravo AF: 0.953

Asia WGS AF: 0.981 AC: 3411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.74
PhyloP100		-0.020
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: rs2473323; hg19: chr1-22389327;