chr1-226995424-C-T

Variant names:

• chr1-226995424-C-T
• rs1343743
• NM_001394014.1:c.4976-444G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.456 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC42BPA	NM_001394014.1	MANE Select	c.4976-444G>A		intron	N/A	NP_001380943.1	Q5VT25-2
	CDC42BPA	NM_001387550.1		c.5249-444G>A		intron	N/A	NP_001374479.1	A0A0A0MRJ1
	CDC42BPA	NM_001366019.2		c.4910-444G>A		intron	N/A	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.4976-444G>A		intron	N/A	ENSP00000355728.5	Q5VT25-2
	CDC42BPA	ENST00000366769.7	TSL:1	c.4871-444G>A		intron	N/A	ENSP00000355731.3	Q5VT25-5
	CDC42BPA	ENST00000366764.8	TSL:1	c.4811-444G>A		intron	N/A	ENSP00000355726.5	A0A0A0MRJ0

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

African (AFR) AF: 0.287 AC: 11908 AN: 41444

American (AMR) AF: 0.334 AC: 5106 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1676 AN: 3472

East Asian (EAS) AF: 0.167 AC: 864 AN: 5176

South Asian (SAS) AF: 0.202 AC: 971 AN: 4818

European-Finnish (FIN) AF: 0.383 AC: 4043 AN: 10550

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31294 AN: 67936

Other (OTH) AF: 0.387 AC: 817 AN: 2110

Alfa AF: 0.430 Hom.: 7640

Bravo AF: 0.373

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1343743; hg19: chr1-227183125;