rs2896463

Variant names:

• chr14-103024555-A-G
• rs2896463
• NM_006035.4:c.176-12367T>C

Variant summary

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

The NM_006035.4(CDC42BPB):​c.176-12367T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,284 control chromosomes in the GnomAD database, including 1,104 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 0.11 (1104 hom., cov: 32)
• Consequence: CDC42BPB NM_006035.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374
• Publications: 1 publications found

Genes affected

CDC42BPB (HGNC:1738): (CDC42 binding protein kinase beta) This gene encodes a member of the serine/threonine protein kinase family. The encoded protein contains a Cdc42/Rac-binding p21 binding domain resembling that of PAK kinase. The kinase domain of this protein is most closely related to that of myotonic dystrophy kinase-related ROK. Studies of the similar gene in rat suggested that this kinase may act as a downstream effector of Cdc42 in cytoskeletal reorganization. [provided by RefSeq, Jul 2008]

CDC42BPB Gene-Disease associations (from GenCC):

• Chilton-Okur-Chung neurodevelopmental syndrome

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006035.4. 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
	CDC42BPB	NM_006035.4	MANE Select	c.176-12367T>C		intron	N/A	NP_006026.3
	CDC42BPB	NM_001411054.1		c.176-12367T>C		intron	N/A	NP_001397983.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC42BPB	ENST00000361246.7	TSL:1 MANE Select	c.176-12367T>C		intron	N/A	ENSP00000355237.2
	CDC42BPB	ENST00000559043.2	TSL:5	c.176-12367T>C		intron	N/A	ENSP00000453384.2

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16896 AN: 152166 Hom.: 1100 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0374

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0899

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.111 AC: 16935 AN: 152284 Hom.: 1104 Cov.: 32 AF XY: 0.110 AC XY: 8163 AN XY: 74464

African (AFR) AF: 0.173 AC: 7191 AN: 41546

American (AMR) AF: 0.101 AC: 1543 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 433 AN: 3472

East Asian (EAS) AF: 0.00231 AC: 12 AN: 5192

South Asian (SAS) AF: 0.0373 AC: 180 AN: 4830

European-Finnish (FIN) AF: 0.112 AC: 1185 AN: 10606

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0899 AC: 6114 AN: 68018

Other (OTH) AF: 0.103 AC: 218 AN: 2114

Alfa AF: 0.0930 Hom.: 403

Bravo AF: 0.112

Asia WGS AF: 0.0390 AC: 134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.46
PhyloP100		0.37
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: rs2896463; hg19: chr14-103490892;