chr3-108554425-T-C

Variant names:

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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 id 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 FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIP2A	NM_020890.3 link	c.2275A>G	p.Ile759Val	missense_variant	Exon 18 of 21	ENST00000295746.13	NP_065941.2	Q8TCG1-1
CIP2A	XM_006713716.4 link	c.2272A>G	p.Ile758Val	missense_variant	Exon 18 of 21		XP_006713779.1
CIP2A	XM_011513057.3 link	c.1333A>G	p.Ile445Val	missense_variant	Exon 11 of 14		XP_011511359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CIP2A	ENST00000295746.13 link	c.2275A>G	p.Ile759Val	missense_variant	Exon 18 of 21	1	NM_020890.3	ENSP00000295746.7	Q8TCG1-1
CIP2A	ENST00000491772.5 link	c.1798A>G	p.Ile600Val	missense_variant	Exon 18 of 21	1		ENSP00000419487.1	Q8TCG1-2
CIP2A	ENST00000481530.5 link	n.*1845A>G		non_coding_transcript_exon_variant	Exon 18 of 21	1		ENSP00000417297.1	F8WAX6
CIP2A	ENST00000481530.5 link	n.*1845A>G		3_prime_UTR_variant	Exon 18 of 21	1		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

Gnomad4 AFR exome

AF:

0.00120

AC:

AN:

32584

Gnomad4 AMR exome

AF:

0.00823

AC:

356

AN:

43272

Gnomad4 ASJ exome

AF:

0.0216

AC:

553

AN:

25660

Gnomad4 EAS exome

AF:

0.0000256

AC:

AN:

39096

Gnomad4 SAS exome

AF:

0.0113

AC:

939

AN:

83140

Gnomad4 FIN exome

AF:

0.0118

AC:

622

AN:

52804

Gnomad4 NFE exome

AF:

0.00922

AC:

9909

AN:

1074208

Gnomad4 Remaining exome

AF:

0.00973

AC:

571

AN:

58676

Heterozygous variant carriers

512

1024

1537

2049

2561

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Gnomad4 AFR

AF:

0.00159

AC:

0.00158715

AN:

0.00158715

Gnomad4 AMR

AF:

0.0103

AC:

0.0102655

AN:

0.0102655

Gnomad4 ASJ

AF:

0.0216

AC:

0.0216014

AN:

0.0216014

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.0128

AC:

0.0128364

AN:

0.0128364

Gnomad4 FIN

AF:

0.0107

AC:

0.0107304

AN:

0.0107304

Gnomad4 NFE

AF:

0.0114

AC:

0.0114375

AN:

0.0114375

Gnomad4 OTH

AF:

0.0137

AC:

0.0137051

AN:

0.0137051

Heterozygous variant carriers

130

195

260

325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CIP2A: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0032

T;.;T

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.028

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.73

T;T;T

MetaRNN

Benign

0.0029

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.16

N;N;.

REVEL

Benign

0.11

Sift

Benign

0.67

T;T;.

Sift4G

Benign

0.36

T;T;T

Polyphen

0.0

B;.;.

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

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