1-227173371-G-A

Variant names:

• chr1-227173371-G-A
• rs1913342
• NM_001394014.1:c.600-12735C>T

Variant summary

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

The NM_001394014.1(CDC42BPA):​c.600-12735C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 152,152 control chromosomes in the GnomAD database, including 54,247 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 0.84 (54247 hom., cov: 31)
• Consequence: CDC42BPA NM_001394014.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.128
• Publications: 8 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394014.1. 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
	CDC42BPA	NM_001394014.1	MANE Select	c.600-12735C>T		intron	N/A	NP_001380943.1
	CDC42BPA	NM_001387550.1		c.600-12735C>T		intron	N/A	NP_001374479.1
	CDC42BPA	NM_001366019.2		c.600-12735C>T		intron	N/A	NP_001352948.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC42BPA	ENST00000366766.8	TSL:5 MANE Select	c.600-12735C>T		intron	N/A	ENSP00000355728.5
	CDC42BPA	ENST00000366769.7	TSL:1	c.600-12735C>T		intron	N/A	ENSP00000355731.3
	CDC42BPA	ENST00000366764.8	TSL:1	c.600-12735C>T		intron	N/A	ENSP00000355726.5

Frequencies

GnomAD3 genomes AF: 0.842 AC: 128052 AN: 152034 Hom.: 54213 Cov.: 31

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.856

Gnomad OTH AF: 0.855

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

GnomAD4 genome AF: 0.842 AC: 128137 AN: 152152 Hom.: 54247 Cov.: 31 AF XY: 0.834 AC XY: 62031 AN XY: 74380

African (AFR) AF: 0.896 AC: 37220 AN: 41538

American (AMR) AF: 0.764 AC: 11674 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 3081 AN: 3472

East Asian (EAS) AF: 0.629 AC: 3244 AN: 5156

South Asian (SAS) AF: 0.790 AC: 3804 AN: 4816

European-Finnish (FIN) AF: 0.756 AC: 7994 AN: 10578

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.856 AC: 58201 AN: 67994

Other (OTH) AF: 0.857 AC: 1806 AN: 2108

Alfa AF: 0.847 Hom.: 30192

Bravo AF: 0.840

Asia WGS AF: 0.751 AC: 2614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.0
DANN	Benign	0.30
PhyloP100		-0.13
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: rs1913342; hg19: chr1-227361072;