1-226995424-C-T

Position:

• chr1-226995424-C-T

Variant summary

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

The NM_001394014.1(CDC42BPA):​c.4976-444G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,986 control chromosomes in the GnomAD database, including 11,498 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 0.38 (11498 hom., cov: 32)
• Consequence: CDC42BPA NM_001394014.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.509

Genes affected

CDC42BPA (HGNC:1737): (CDC42 binding protein kinase alpha) The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase contains multiple functional domains. Its kinase domain is highly similar to that of the myotonic dystrophy protein kinase (DMPK). This kinase also contains a Rac interactive binding (CRIB) domain, and has been shown to bind CDC42. It may function as a CDC42 downstream effector mediating CDC42 induced peripheral actin formation, and promoting cytoskeletal reorganization. Multiple alternatively spliced transcript variants have been described. [provided by RefSeq, Sep 2018]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC42BPA	NM_001394014.1	c.4976-444G>A		intron_variant		ENST00000366766.8	NP_001380943.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC42BPA	ENST00000366766.8	c.4976-444G>A		intron_variant		5	NM_001394014.1	ENSP00000355728

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57386 AN: 151868 Hom.: 11496 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.378 AC: 57402 AN: 151986 Hom.: 11498 Cov.: 32 AF XY: 0.369 AC XY: 27436 AN XY: 74300

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.387

Alfa AF: 0.427 Hom.: 6809

Bravo AF: 0.373

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1343743; hg19: chr1-227183125;