Variant 1-226994973-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001394014.1(CDC42BPA):c.4983C>T(p.Ser1661=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00421 in 1,613,718 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 10 hom., cov: 33)

Exomes 𝑓: 0.0042 ( 88 hom. )

Consequence

CDC42BPA
NM_001394014.1 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.95

Variant links:

Genes affected

CDC42BPA (HGNC:1737): (CDC42 binding protein kinase alpha) The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase contains multiple functional domains. Its kinase domain is highly similar to that of the myotonic dystrophy protein kinase (DMPK). This kinase also contains a Rac interactive binding (CRIB) domain, and has been shown to bind CDC42. It may function as a CDC42 downstream effector mediating CDC42 induced peripheral actin formation, and promoting cytoskeletal reorganization. Multiple alternatively spliced transcript variants have been described. [provided by RefSeq, Sep 2018]

CDC42BPA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 1-226994973-G-A is Benign according to our data. Variant chr1-226994973-G-A is described in ClinVar as [Benign]. Clinvar id is 790636.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.95 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00389 (593/152268) while in subpopulation EAS AF= 0.047 (243/5174). AF 95% confidence interval is 0.0421. There are 10 homozygotes in gnomad4. There are 331 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 593 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC42BPA	NM_001394014.1 linkuse as main transcript	c.4983C>T	p.Ser1661=	synonymous_variant	36/37	ENST00000366766.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC42BPA	ENST00000366766.8 linkuse as main transcript	c.4983C>T	p.Ser1661=	synonymous_variant	36/37	5	NM_001394014.1		Q5VT25-2

Frequencies

GnomAD3 genomes

AF:

0.00390

AC:

593

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0469

Gnomad SAS

AF:

0.0218

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00287

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00821

AC:

2058

AN:

250682

Hom.:

AF XY:

0.00844

AC XY:

1144

AN XY:

135468

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000522

Gnomad ASJ exome

AF:

0.000898

Gnomad EAS exome

AF:

0.0526

Gnomad SAS exome

AF:

0.0219

Gnomad FIN exome

AF:

0.00116

Gnomad NFE exome

AF:

0.00290

Gnomad OTH exome

AF:

0.00589

GnomAD4 exome

AF:

0.00424

AC:

6196

AN:

1461450

Hom.:

Cov.:

AF XY:

0.00467

AC XY:

3393

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000560

Gnomad4 ASJ exome

AF:

0.000919

Gnomad4 EAS exome

AF:

0.0362

Gnomad4 SAS exome

AF:

0.0198

Gnomad4 FIN exome

AF:

0.00116

Gnomad4 NFE exome

AF:

0.00234

Gnomad4 OTH exome

AF:

0.00540

GnomAD4 genome

AF:

0.00389

AC:

593

AN:

152268

Hom.:

Cov.:

AF XY:

0.00445

AC XY:

331

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0470

Gnomad4 SAS

AF:

0.0218

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00287

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00232

Hom.:

Bravo

AF:

0.00359

Asia WGS

AF:

0.0350

AC:

122

AN:

3478

EpiCase

AF:

0.00158

EpiControl

AF:

0.00172

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.16

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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