Variant 3-108579413-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020890.3(CIP2A):c.686G>A(p.Arg229Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,605,506 control chromosomes in the GnomAD database, including 16,017 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.13 ( 1695 hom., cov: 32)

Exomes 𝑓: 0.12 ( 14322 hom. )

Consequence

CIP2A
NM_020890.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.58

Variant links:

Genes affected

CIP2A (HGNC:29302): (cellular inhibitor of PP2A) Enables protein homodimerization activity. Predicted to act upstream of or within positive regulation of neural precursor cell proliferation and spermatogenesis. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CIP2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012404919).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIP2A	NM_020890.3 linkuse as main transcript	c.686G>A	p.Arg229Gln	missense_variant	7/21	ENST00000295746.13
CIP2A	XM_006713716.4 linkuse as main transcript	c.683G>A	p.Arg228Gln	missense_variant	7/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIP2A	ENST00000295746.13 linkuse as main transcript	c.686G>A	p.Arg229Gln	missense_variant	7/21	1	NM_020890.3	P1	Q8TCG1-1
CIP2A	ENST00000491772.5 linkuse as main transcript	c.209G>A	p.Arg70Gln	missense_variant	7/21	1			Q8TCG1-2
CIP2A	ENST00000487834.5 linkuse as main transcript	n.955G>A		non_coding_transcript_exon_variant	7/14	1
CIP2A	ENST00000481530.5 linkuse as main transcript	c.*256G>A		3_prime_UTR_variant, NMD_transcript_variant	7/21	1

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19345

AN:

151808

Hom.:

1692

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0999

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.133

Gnomad EAS

AF:

0.524

Gnomad SAS

AF:

0.123

Gnomad FIN

AF:

0.154

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.128

GnomAD3 exomes

AF:

0.157

AC:

39020

AN:

248906

Hom.:

4729

AF XY:

0.151

AC XY:

20353

AN XY:

134848

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.204

Gnomad ASJ exome

AF:

0.127

Gnomad EAS exome

AF:

0.533

Gnomad SAS exome

AF:

0.120

Gnomad FIN exome

AF:

0.144

Gnomad NFE exome

AF:

0.105

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.120

AC:

174261

AN:

1453580

Hom.:

14322

Cov.:

AF XY:

0.119

AC XY:

86272

AN XY:

723328

show subpopulations

Gnomad4 AFR exome

AF:

0.0940

Gnomad4 AMR exome

AF:

0.200

Gnomad4 ASJ exome

AF:

0.127

Gnomad4 EAS exome

AF:

0.526

Gnomad4 SAS exome

AF:

0.116

Gnomad4 FIN exome

AF:

0.140

Gnomad4 NFE exome

AF:

0.101

Gnomad4 OTH exome

AF:

0.134

GnomAD4 genome

AF:

0.127

AC:

19358

AN:

151926

Hom.:

1695

Cov.:

AF XY:

0.131

AC XY:

9745

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.0997

Gnomad4 AMR

AF:

0.157

Gnomad4 ASJ

AF:

0.133

Gnomad4 EAS

AF:

0.525

Gnomad4 SAS

AF:

0.123

Gnomad4 FIN

AF:

0.154

Gnomad4 NFE

AF:

0.103

Gnomad4 OTH

AF:

0.131

Alfa

AF:

0.119

Hom.:

3136

Bravo

AF:

0.130

TwinsUK

AF:

0.113

AC:

418

ALSPAC

AF:

0.102

AC:

392

ESP6500AA

AF:

0.0922

AC:

405

ESP6500EA

AF:

0.103

AC:

889

ExAC

AF:

0.152

AC:

18492

Asia WGS

AF:

0.289

AC:

1002

AN:

3472

EpiCase

AF:

0.103

EpiControl

AF:

0.100

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0035

T;.;T

Eigen

Benign

0.099

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.88

D;D;D

MetaRNN

Benign

0.0012

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.8

L;.;.

MutationTaster

Benign

0.0052

P;P

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.2

N;N;.

REVEL

Benign

0.066

Sift

Uncertain

0.016

D;D;.

Sift4G

Uncertain

0.037

D;D;D

Polyphen

0.14

B;.;.

Vest4

0.070

MPC

0.19

ClinPred

0.017

GERP RS

5.1

Varity_R

0.48

gMVP

0.12

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over