14-102933761-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_006035.4(CDC42BPB):c.5087G>A(p.Arg1696Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000387 in 1,498,892 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1696G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000038 ( 1 hom. )

Consequence

CDC42BPB
NM_006035.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.80

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:

AMN (HGNC:14604): (amnion associated transmembrane protein) The protein encoded by this gene is a type I transmembrane protein. It is thought to modulate bone morphogenetic protein (BMP) receptor function by serving as an accessory or coreceptor, and thus facilitates or hinders BMP binding. It is known that the mouse AMN gene is expressed in the extraembryonic visceral endoderm layer during gastrulation, but it is found to be mutated in amnionless mouse. The encoded protein has sequence similarity to short gastrulation (Sog) and procollagen IIA proteins in Drosophila. [provided by RefSeq, Jul 2008]

AMN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.037265986).

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000461 (7/151744) while in subpopulation SAS AF= 0.00126 (6/4774). AF 95% confidence interval is 0.000547. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC42BPB	NM_006035.4 link	c.5087G>A	p.Arg1696Lys	missense_variant	Exon 37 of 37	ENST00000361246.7	NP_006026.3	Q9Y5S2A0A024R6N2Q86XZ8
CDC42BPB	NM_001411054.1 link	c.5009G>A	p.Arg1670Lys	missense_variant	Exon 36 of 36		NP_001397983.1
CDC42BPB	XM_005268227.2 link	c.5138G>A	p.Arg1713Lys	missense_variant	Exon 38 of 38		XP_005268284.1
CDC42BPB	XM_005268228.2 link	c.5060G>A	p.Arg1687Lys	missense_variant	Exon 37 of 37		XP_005268285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CDC42BPB	ENST00000361246.7 link	c.5087G>A	p.Arg1696Lys	missense_variant	Exon 37 of 37	1	NM_006035.4	ENSP00000355237.2	Q9Y5S2
CDC42BPB	ENST00000559043.2 link	c.5009G>A	p.Arg1670Lys	missense_variant	Exon 36 of 36	5		ENSP00000453384.2	H0YLY0
ENSG00000259515	ENST00000560931.1 link	n.188C>T		non_coding_transcript_exon_variant	Exon 1 of 2	3
AMN	ENST00000558590.1 link	n.*165C>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000461

AC:

AN:

151744

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:

0.00

Gnomad SAS

AF:

0.00126

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000846

AC:

AN:

129960

Hom.:

AF XY:

0.000124

AC XY:

AN XY:

72480

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000536

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000147

Gnomad OTH exome

AF:

0.000734

GnomAD4 exome

AF:

0.0000379

AC:

AN:

1347148

Hom.:

Cov.:

AF XY:

0.0000465

AC XY:

AN XY:

666086

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000476

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000112

Gnomad4 OTH exome

AF:

0.000126

GnomAD4 genome

AF:

0.0000461

AC:

AN:

151744

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74074

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00126

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000436

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000667

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CDC42BPB: PP2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.033

Eigen

Benign

-0.14

Eigen_PC

Benign

0.043

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.79

M_CAP

Benign

0.052

MetaRNN

Benign

0.037

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.4

PrimateAI

Uncertain

0.67

PROVEAN

Benign

0.23

REVEL

Benign

0.14

Sift

Benign

0.29

Sift4G

Benign

0.82

Polyphen

0.15

Vest4

0.23

MutPred

0.14

Gain of ubiquitination at R1696 (P = 0.0039);

MVP

0.60

MPC

1.3

ClinPred

0.072

GERP RS

4.9

Varity_R

0.25

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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