rs1106679

Variant names:

• chr14-103019315-A-G
• rs1106679
• NM_006035.4:c.176-7127T>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.176-7127T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,076 control chromosomes in the GnomAD database, including 5,931 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 (5931 hom., cov: 32)
• Consequence: CDC42BPB NM_006035.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.687
• Publications: 7 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=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC42BPB	NM_006035.4	c.176-7127T>C		intron_variant	Intron 1 of 36	ENST00000361246.7	NP_006026.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC42BPB	ENST00000361246.7	c.176-7127T>C		intron_variant	Intron 1 of 36	1	NM_006035.4	ENSP00000355237.2
CDC42BPB	ENST00000559043.2	c.176-7127T>C		intron_variant	Intron 1 of 35	5		ENSP00000453384.2

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33024 AN: 151958 Hom.: 5904 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.0525

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.218 AC: 33108 AN: 152076 Hom.: 5931 Cov.: 32 AF XY: 0.213 AC XY: 15814 AN XY: 74342

African (AFR) AF: 0.495 AC: 20501 AN: 41438

American (AMR) AF: 0.145 AC: 2210 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 554 AN: 3468

East Asian (EAS) AF: 0.0135 AC: 70 AN: 5180

South Asian (SAS) AF: 0.0523 AC: 252 AN: 4814

European-Finnish (FIN) AF: 0.136 AC: 1438 AN: 10594

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.111 AC: 7558 AN: 67980

Other (OTH) AF: 0.183 AC: 386 AN: 2114

Alfa AF: 0.182 Hom.: 706

Bravo AF: 0.228

Asia WGS AF: 0.0710 AC: 247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.79
DANN	Benign	0.22
PhyloP100		-0.69
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: rs1106679; hg19: chr14-103485652;