rs872945

Variant names:

• chr14-103009321-A-G
• rs872945
• NM_006035.4:c.268-766T>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.268-766T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,244 control chromosomes in the GnomAD database, including 5,441 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 0.24 (5441 hom., cov: 33)
• Consequence: CDC42BPB NM_006035.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC42BPB	NM_006035.4	c.268-766T>C		intron_variant	Intron 2 of 36	ENST00000361246.7	NP_006026.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC42BPB	ENST00000361246.7	c.268-766T>C		intron_variant	Intron 2 of 36	1	NM_006035.4	ENSP00000355237.2
CDC42BPB	ENST00000559043.2	c.268-766T>C		intron_variant	Intron 2 of 35	5		ENSP00000453384.2

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36333 AN: 152126 Hom.: 5442 Cov.: 33

Gnomad AFR AF: 0.0672

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.239 AC: 36326 AN: 152244 Hom.: 5441 Cov.: 33 AF XY: 0.240 AC XY: 17899 AN XY: 74440

African (AFR) AF: 0.0674 AC: 2800 AN: 41570

American (AMR) AF: 0.232 AC: 3554 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1304 AN: 3472

East Asian (EAS) AF: 0.106 AC: 548 AN: 5180

South Asian (SAS) AF: 0.326 AC: 1571 AN: 4826

European-Finnish (FIN) AF: 0.303 AC: 3210 AN: 10592

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22411 AN: 67994

Other (OTH) AF: 0.265 AC: 559 AN: 2112

Alfa AF: 0.304 Hom.: 12242

Bravo AF: 0.221

Asia WGS AF: 0.216 AC: 753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.31
PhyloP100		2.0
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: rs872945; hg19: chr14-103475658;