1-227059459-A-T

Variant names:

• chr1-227059459-A-T
• rs10495265
• NM_001394014.1:c.2905-7474T>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.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
• Publications: 3 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=-0.64).
• 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 rank	MANE	Protein	UniProt
CDC42BPA	NM_001394014.1	c.2905-7474T>A		intron_variant	Intron 21 of 36	ENST00000366766.8	NP_001380943.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC42BPA	ENST00000366766.8	c.2905-7474T>A		intron_variant	Intron 21 of 36	5	NM_001394014.1	ENSP00000355728.5

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

GnomAD2 exomes AF: 0.0826 AC: 12616 AN: 152804 AF XY: 0.0849

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 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

African (AFR) AF: 0.0166 AC: 501 AN: 30140

American (AMR) AF: 0.0764 AC: 2723 AN: 35622

Ashkenazi Jewish (ASJ) AF: 0.0843 AC: 2083 AN: 24702

East Asian (EAS) AF: 0.151 AC: 5353 AN: 35490

South Asian (SAS) AF: 0.105 AC: 8164 AN: 77710

European-Finnish (FIN) AF: 0.0655 AC: 3164 AN: 48308

Middle Eastern (MID) AF: 0.120 AC: 667 AN: 5558

European-Non Finnish (NFE) AF: 0.0740 AC: 74793 AN: 1011042

Other (OTH) AF: 0.0772 AC: 4301 AN: 55746

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

African (AFR) AF: 0.0172 AC: 717 AN: 41586

American (AMR) AF: 0.0893 AC: 1366 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0761 AC: 264 AN: 3470

East Asian (EAS) AF: 0.154 AC: 797 AN: 5180

South Asian (SAS) AF: 0.111 AC: 537 AN: 4830

European-Finnish (FIN) AF: 0.0601 AC: 638 AN: 10622

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0753 AC: 5123 AN: 68022

Other (OTH) AF: 0.0833 AC: 176 AN: 2112

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
PhyloP100		0.61
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: rs10495265; hg19: chr1-227247160;