1-227029074-C-G

Variant names:

• chr1-227029074-C-G
• rs1929860
• NM_001394014.1:c.4015G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001394014.1(CDC42BPA):​c.4015G>C​(p.Val1339Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDC42BPA NM_001394014.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.262
• Publications: 32 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047837436).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC42BPA	NM_001394014.1	MANE Select	c.4015G>C	p.Val1339Leu	missense	Exon 30 of 37	NP_001380943.1	Q5VT25-2
	CDC42BPA	NM_001387550.1		c.4102G>C	p.Val1368Leu	missense	Exon 32 of 40	NP_001374479.1	A0A0A0MRJ1
	CDC42BPA	NM_001366019.2		c.3949G>C	p.Val1317Leu	missense	Exon 30 of 37	NP_001352948.1	Q5VT25-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC42BPA	ENST00000366766.8	TSL:5 MANE Select	c.4015G>C	p.Val1339Leu	missense	Exon 30 of 37	ENSP00000355728.5	Q5VT25-2
	CDC42BPA	ENST00000366769.7	TSL:1	c.3910G>C	p.Val1304Leu	missense	Exon 29 of 36	ENSP00000355731.3	Q5VT25-5
	CDC42BPA	ENST00000366764.8	TSL:1	c.3850G>C	p.Val1284Leu	missense	Exon 29 of 36	ENSP00000355726.5	A0A0A0MRJ0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.034	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.2	N
PhyloP100		0.26
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.40	N
REVEL	Benign	0.12
Sift	Benign	0.63	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.62		Loss of sheet (P = 0.003)
MVP		0.17
MPC		0.23
ClinPred		0.23	T
GERP RS		4.2
Varity_R		0.053
gMVP		0.21
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1929860; hg19: chr1-227216775;