1-22068132-A-G

Variant names:

• chr1-22068132-A-G
• rs17837965
• NM_001791.4:c.-50-10297A>G

Variant summary

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

The NM_001791.4(CDC42):​c.-50-10297A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0555 in 152,250 control chromosomes in the GnomAD database, including 376 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 0.056 (376 hom., cov: 32)
• Consequence: CDC42 NM_001791.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740
• Publications: 10 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:):

MPHOSPH6P1 (HGNC:54549): (MPHOSPH6 pseudogene 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001791.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC42	NM_001791.4	MANE Select	c.-50-10297A>G		intron	N/A	NP_001782.1
	CDC42	NM_001039802.2		c.-176-5962A>G		intron	N/A	NP_001034891.1
	CDC42	NM_044472.3		c.-50-10297A>G		intron	N/A	NP_426359.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC42	ENST00000656825.1	MANE Select	c.-50-10297A>G		intron	N/A	ENSP00000499457.1
	CDC42	ENST00000315554.15	TSL:1	c.-50-10297A>G		intron	N/A	ENSP00000314458.8
	CDC42	ENST00000344548.8	TSL:1	c.-176-5962A>G		intron	N/A	ENSP00000341072.3

Frequencies

GnomAD3 genomes AF: 0.0556 AC: 8459 AN: 152132 Hom.: 377 Cov.: 32

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0922

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0495

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0543

Gnomad OTH AF: 0.0588

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

GnomAD4 genome AF: 0.0555 AC: 8453 AN: 152250 Hom.: 376 Cov.: 32 AF XY: 0.0592 AC XY: 4407 AN XY: 74456

African (AFR) AF: 0.0104 AC: 432 AN: 41570

American (AMR) AF: 0.117 AC: 1782 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0922 AC: 320 AN: 3470

East Asian (EAS) AF: 0.121 AC: 626 AN: 5178

South Asian (SAS) AF: 0.0498 AC: 240 AN: 4822

European-Finnish (FIN) AF: 0.103 AC: 1089 AN: 10608

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0543 AC: 3690 AN: 68008

Other (OTH) AF: 0.0582 AC: 123 AN: 2114

Alfa AF: 0.0600 Hom.: 223

Bravo AF: 0.0549

Asia WGS AF: 0.0790 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.84
PhyloP100		-0.074
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: rs17837965; hg19: chr1-22394625;