rs751837

Positions:

• chr14-103018488-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC42BPB	NM_006035.4	c.176-6300A>G		intron_variant		ENST00000361246.7	NP_006026.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC42BPB	ENST00000361246.7	c.176-6300A>G		intron_variant		1	NM_006035.4	ENSP00000355237	P1
CDC42BPB	ENST00000559043.2	c.176-6300A>G		intron_variant		5		ENSP00000453384

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

Gnomad4 AFR AF: 0.493

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.0135

Gnomad4 SAS AF: 0.0525

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.181

Alfa AF: 0.119 Hom.: 3118

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	-1.0
CADD	Benign	0.25
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs751837; hg19: chr14-103484825;