1-227059459-A-T

Position:

• chr1-227059459-A-T

Variant summary

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

The NM_001394014.1(CDC42BPA):​c.2905-7474T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0754 in 1,476,646 control chromosomes in the GnomAD database, including 4,888 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 0.063 (401 hom., cov: 32)
  • Exomes 𝑓: 0.077 (4487 hom.)
• Consequence: CDC42BPA NM_001394014.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.606

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=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC42BPA	NM_001394014.1	c.2905-7474T>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.2905-7474T>A		intron_variant		5	NM_001394014.1	ENSP00000355728

Frequencies

GnomAD3 genomes AF: 0.0634 AC: 9656 AN: 152210 Hom.: 397 Cov.: 32

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0895

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0601

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0753

Gnomad OTH AF: 0.0756

GnomAD3 exomes AF: 0.0826 AC: 12616 AN: 152804 Hom.: 602 AF XY: 0.0849 AC XY: 6939 AN XY: 81700

Gnomad AFR exome AF: 0.0155

Gnomad AMR exome AF: 0.0799

Gnomad ASJ exome AF: 0.0851

Gnomad EAS exome AF: 0.142

Gnomad SAS exome AF: 0.107

Gnomad FIN exome AF: 0.0656

Gnomad NFE exome AF: 0.0761

Gnomad OTH exome AF: 0.0803

GnomAD4 exome AF: 0.0768 AC: 101749 AN: 1324318 Hom.: 4487 Cov.: 21 AF XY: 0.0780 AC XY: 51315 AN XY: 657486

Gnomad4 AFR exome AF: 0.0166

Gnomad4 AMR exome AF: 0.0764

Gnomad4 ASJ exome AF: 0.0843

Gnomad4 EAS exome AF: 0.151

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.0655

Gnomad4 NFE exome AF: 0.0740

Gnomad4 OTH exome AF: 0.0772

GnomAD4 genome AF: 0.0634 AC: 9663 AN: 152328 Hom.: 401 Cov.: 32 AF XY: 0.0648 AC XY: 4825 AN XY: 74484

Gnomad4 AFR AF: 0.0172

Gnomad4 AMR AF: 0.0893

Gnomad4 ASJ AF: 0.0761

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.0601

Gnomad4 NFE AF: 0.0753

Gnomad4 OTH AF: 0.0833

Alfa AF: 0.0401 Hom.: 43

Bravo AF: 0.0594

Asia WGS AF: 0.140 AC: 490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.2
DANN	Benign	0.80

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: rs10495265; hg19: chr1-227247160;