NM_006035.4:c.176-6300A>G

Variant names:

• chr14-103018488-T-C
• rs751837
• NM_006035.4:c.176-6300A>G

Variant summary

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

The NM_006035.4(CDC42BPB):​c.176-6300A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,064 control chromosomes in the GnomAD database, including 5,900 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 0.22 (5900 hom., cov: 32)
• Consequence: CDC42BPB NM_006035.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.50
• Publications: 24 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.488 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC42BPB	NM_006035.4	MANE Select	c.176-6300A>G		intron	N/A	NP_006026.3
	CDC42BPB	NM_001411054.1		c.176-6300A>G		intron	N/A	NP_001397983.1	H0YLY0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC42BPB	ENST00000361246.7	TSL:1 MANE Select	c.176-6300A>G		intron	N/A	ENSP00000355237.2	Q9Y5S2
	CDC42BPB	ENST00000901190.1		c.176-6300A>G		intron	N/A	ENSP00000571249.1
	CDC42BPB	ENST00000901191.1		c.176-6300A>G		intron	N/A	ENSP00000571250.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32960 AN: 151948 Hom.: 5872 Cov.: 32

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.0527

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.217 AC: 33044 AN: 152064 Hom.: 5900 Cov.: 32 AF XY: 0.212 AC XY: 15791 AN XY: 74322

African (AFR) AF: 0.493 AC: 20435 AN: 41430

American (AMR) AF: 0.145 AC: 2210 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 553 AN: 3468

East Asian (EAS) AF: 0.0135 AC: 70 AN: 5184

South Asian (SAS) AF: 0.0525 AC: 253 AN: 4816

European-Finnish (FIN) AF: 0.136 AC: 1443 AN: 10576

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7558 AN: 67988

Other (OTH) AF: 0.181 AC: 382 AN: 2110

Alfa AF: 0.137 Hom.: 9721

Bravo AF: 0.228

Asia WGS AF: 0.0710 AC: 247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.56
PhyloP100		-5.5
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: rs751837; hg19: chr14-103484825;