dbSNP rs13071874: CIP2A:p.Ile759Val (chr3-108554425-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_020890.3(CIP2A):c.2275A>G(p.Ile759Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00921 in 1,567,210 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0085 ( 8 hom., cov: 31)

Exomes 𝑓: 0.0093 ( 101 hom. )

Consequence

CIP2A
NM_020890.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.574

Publications

9 publications found

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 was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028879046).

BP6

Variant 3-108554425-T-C is Benign according to our data. Variant chr3-108554425-T-C is described in ClinVar as Benign. ClinVar VariationId is 2654025.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00929 (13143/1414870) while in subpopulation MID AF = 0.0282 (153/5430). AF 95% confidence interval is 0.0245. There are 101 homozygotes in GnomAdExome4. There are 6722 alleles in the male GnomAdExome4 subpopulation. Median coverage is 24. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020890.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIP2A	NM_020890.3	MANE Select	c.2275A>G	p.Ile759Val	missense	Exon 18 of 21	NP_065941.2	Q8TCG1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CIP2A	ENST00000295746.13	TSL:1 MANE Select	c.2275A>G	p.Ile759Val	missense	Exon 18 of 21	ENSP00000295746.7	Q8TCG1-1
CIP2A	ENST00000491772.5	TSL:1	c.1798A>G	p.Ile600Val	missense	Exon 18 of 21	ENSP00000419487.1	Q8TCG1-2
CIP2A	ENST00000481530.5	TSL:1	n.*1845A>G		non_coding_transcript_exon	Exon 18 of 21	ENSP00000417297.1	F8WAX6

Frequencies

GnomAD3 genomes

AF:

0.00849

AC:

1293

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00159

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0128

Gnomad FIN

AF:

0.0107

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.0138

GnomAD2 exomes

AF:

0.00977

AC:

2276

AN:

233056

AF XY:

0.0106

show subpopulations

Gnomad AFR exome

AF:

0.00122

Gnomad AMR exome

AF:

0.00759

Gnomad ASJ exome

AF:

0.0221

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0121

Gnomad NFE exome

AF:

0.0116

Gnomad OTH exome

AF:

0.0118

GnomAD4 exome

AF:

0.00929

AC:

13143

AN:

1414870

Hom.:

101

Cov.:

AF XY:

0.00954

AC XY:

6722

AN XY:

704944

show subpopulations

African (AFR)

AF:

0.00120

AC:

AN:

32584

American (AMR)

AF:

0.00823

AC:

356

AN:

43272

Ashkenazi Jewish (ASJ)

AF:

0.0216

AC:

553

AN:

25660

East Asian (EAS)

AF:

0.0000256

AC:

AN:

39096

South Asian (SAS)

AF:

0.0113

AC:

939

AN:

83140

European-Finnish (FIN)

AF:

0.0118

AC:

622

AN:

52804

Middle Eastern (MID)

AF:

0.0282

AC:

153

AN:

5430

European-Non Finnish (NFE)

AF:

0.00922

AC:

9909

AN:

1074208

Other (OTH)

AF:

0.00973

AC:

571

AN:

58676

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

512

1024

1537

2049

2561

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

318

636

954

1272

1590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00849

AC:

1293

AN:

152340

Hom.:

Cov.:

AF XY:

0.00860

AC XY:

641

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.00159

AC:

AN:

41584

American (AMR)

AF:

0.0103

AC:

157

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0216

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.0128

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0107

AC:

114

AN:

10624

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0114

AC:

778

AN:

68022

Other (OTH)

AF:

0.0137

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

130

195

260

325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0106

Hom.:

Bravo

AF:

0.00830

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00986

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0112

AC:

ExAC

AF:

0.00899

AC:

1090

Asia WGS

AF:

0.00578

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0032

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.028

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0029

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

0.57

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.16

REVEL

Benign

0.11

Sift

Benign

0.67

Sift4G

Benign

0.36

Polyphen

0.0

Vest4

0.051

MVP

0.41

MPC

0.12

ClinPred

0.0057

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.029

gMVP

0.049

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over