1-22084526-T-G

Position:

• chr1-22084526-T-G

Variant summary

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

The NM_001791.4(CDC42):​c.179-1913T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 150,804 control chromosomes in the GnomAD database, including 44,236 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 0.77 (44236 hom., cov: 26)
• Consequence: CDC42 NM_001791.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.938

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC42	NM_001791.4	c.179-1913T>G		intron_variant		ENST00000656825.1	NP_001782.1
CDC42	NM_001039802.2	c.179-1913T>G		intron_variant			NP_001034891.1
CDC42	NM_044472.3	c.179-1913T>G		intron_variant			NP_426359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC42	ENST00000656825.1	c.179-1913T>G		intron_variant			NM_001791.4	ENSP00000499457.1
ENSG00000289694	ENST00000695855.1	c.179-1913T>G		intron_variant				ENSP00000512220.1

Frequencies

GnomAD3 genomes AF: 0.765 AC: 115330 AN: 150686 Hom.: 44216 Cov.: 26

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.765

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

GnomAD4 genome AF: 0.765 AC: 115389 AN: 150804 Hom.: 44236 Cov.: 26 AF XY: 0.766 AC XY: 56416 AN XY: 73642

Gnomad4 AFR AF: 0.757

Gnomad4 AMR AF: 0.747

Gnomad4 ASJ AF: 0.754

Gnomad4 EAS AF: 0.878

Gnomad4 SAS AF: 0.881

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.767

Alfa AF: 0.681 Hom.: 1970

Bravo AF: 0.765

Asia WGS AF: 0.869 AC: 3013 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.56
DANN	Benign	0.34

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: rs2473316; hg19: chr1-22411019;