14-102933747-G-A

Position:

chr14-102933747-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_006035.4(CDC42BPB):c.5101C>T(p.Leu1701Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000014 in 1,494,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

CDC42BPB
NM_006035.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 3.23

Variant links:

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 links:

ENSG00000259515 (HGNC:):

ENSG00000259515 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CDC42BPB. . Gene score misZ 3.6598 (greater than the threshold 3.09). Trascript score misZ 3.9995 (greater than threshold 3.09). GenCC has associacion of gene with Chilton-Okur-Chung neurodevelopmental syndrome, complex neurodevelopmental disorder.

BP4

Computational evidence support a benign effect (MetaRNN=0.20164773).

BS2

High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC42BPB	NM_006035.4 linkuse as main transcript	c.5101C>T	p.Leu1701Phe	missense_variant	37/37	ENST00000361246.7	NP_006026.3	Q9Y5S2A0A024R6N2Q86XZ8
CDC42BPB	NM_001411054.1 linkuse as main transcript	c.5023C>T	p.Leu1675Phe	missense_variant	36/36		NP_001397983.1
CDC42BPB	XM_005268227.2 linkuse as main transcript	c.5152C>T	p.Leu1718Phe	missense_variant	38/38		XP_005268284.1
CDC42BPB	XM_005268228.2 linkuse as main transcript	c.5074C>T	p.Leu1692Phe	missense_variant	37/37		XP_005268285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CDC42BPB	ENST00000361246.7 linkuse as main transcript	c.5101C>T	p.Leu1701Phe	missense_variant	37/37	1	NM_006035.4	ENSP00000355237.2	Q9Y5S2
CDC42BPB	ENST00000559043.2 linkuse as main transcript	c.5023C>T	p.Leu1675Phe	missense_variant	36/36	5		ENSP00000453384.2	H0YLY0
ENSG00000259515	ENST00000560931.1 linkuse as main transcript	n.174G>A		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000236

AC:

AN:

127124

Hom.:

AF XY:

0.0000141

AC XY:

AN XY:

71064

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000152

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000150

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000134

AC:

AN:

1342480

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

663462

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000446

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000150

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000122

Gnomad4 OTH exome

AF:

0.0000540

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CDC42BPB-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 03, 2024

The CDC42BPB c.5101C>T variant is predicted to result in the amino acid substitution p.Leu1701Phe. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.058

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.46

MutationAssessor

Uncertain

2.7

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.49

REVEL

Uncertain

0.32

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.010

Polyphen

0.96

Vest4

0.31

MutPred

0.095

Gain of loop (P = 0.1069);

MVP

0.64

MPC

0.74

ClinPred

0.50

GERP RS

3.0

Varity_R

0.045

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over