Genetic Variant CINP:p.Arg164His (chr14-102348705-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032630.3(CINP):c.491G>A(p.Arg164His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,613,156 control chromosomes in the GnomAD database, including 61,508 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 0.22 ( 4160 hom., cov: 32)

Exomes 𝑓: 0.27 ( 57348 hom. )

Consequence

CINP
NM_032630.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.667

Publications

36 publications found

Variant links:

Genes affected

CINP (HGNC:23789): (cyclin dependent kinase 2 interacting protein) The protein encoded by this gene is reported to be a component of the DNA replication complex as well as a genome-maintenance protein. It may interact with proteins important for replication initiation and has been shown to bind chromatin at the G1 phase of the cell cycle and dissociate from chromatin with replication initiation. It may also serve to regulate checkpoint signaling as part of the DNA damage response. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

CINP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00581488).

BP6

Variant 14-102348705-C-T is Benign according to our data. Variant chr14-102348705-C-T is described in ClinVar as Benign. ClinVar VariationId is 1251504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CINP	NM_032630.3 link	c.491G>A	p.Arg164His	missense_variant	Exon 5 of 5	ENST00000216756.11	NP_116019.1	Q9BW66-1A0A024R6M9
CINP	NM_001320046.2 link	c.*4G>A		3_prime_UTR_variant	Exon 4 of 4		NP_001306975.1	Q9BW66-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CINP	ENST00000216756.11 link	c.491G>A	p.Arg164His	missense_variant	Exon 5 of 5	1	NM_032630.3	ENSP00000216756.6		Q9BW66-1

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

32932

AN:

152072

Hom.:

4153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.217

Gnomad ASJ

AF:

0.353

Gnomad EAS

AF:

0.0948

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.170

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.234

GnomAD2 exomes

AF:

0.236

AC:

58846

AN:

249500

AF XY:

0.243

show subpopulations

Gnomad AFR exome

AF:

0.0941

Gnomad AMR exome

AF:

0.184

Gnomad ASJ exome

AF:

0.357

Gnomad EAS exome

AF:

0.0823

Gnomad FIN exome

AF:

0.182

Gnomad NFE exome

AF:

0.294

Gnomad OTH exome

AF:

0.272

GnomAD4 exome

AF:

0.274

AC:

400629

AN:

1460966

Hom.:

57348

Cov.:

AF XY:

0.274

AC XY:

198840

AN XY:

726714

show subpopulations

African (AFR)

AF:

0.0938

AC:

3138

AN:

33472

American (AMR)

AF:

0.188

AC:

8376

AN:

44618

Ashkenazi Jewish (ASJ)

AF:

0.352

AC:

9187

AN:

26098

East Asian (EAS)

AF:

0.108

AC:

4290

AN:

39676

South Asian (SAS)

AF:

0.236

AC:

20344

AN:

86126

European-Finnish (FIN)

AF:

0.181

AC:

9639

AN:

53348

Middle Eastern (MID)

AF:

0.325

AC:

1875

AN:

5764

European-Non Finnish (NFE)

AF:

0.295

AC:

327518

AN:

1111508

Other (OTH)

AF:

0.269

AC:

16262

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

16485

32970

49456

65941

82426

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10622

21244

31866

42488

53110

<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:

0.217

AC:

32960

AN:

152190

Hom.:

4160

Cov.:

AF XY:

0.212

AC XY:

15772

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.102

AC:

4241

AN:

41550

American (AMR)

AF:

0.218

AC:

3330

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.353

AC:

1226

AN:

3470

East Asian (EAS)

AF:

0.0946

AC:

490

AN:

5180

South Asian (SAS)

AF:

0.232

AC:

1118

AN:

4822

European-Finnish (FIN)

AF:

0.170

AC:

1800

AN:

10592

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.295

AC:

20043

AN:

67964

Other (OTH)

AF:

0.232

AC:

489

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1304

2607

3911

5214

6518

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

340

680

1020

1360

1700

<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:

0.264

Hom.:

14396

Bravo

AF:

0.211

TwinsUK

AF:

0.299

AC:

1110

ALSPAC

AF:

0.292

AC:

1125

ESP6500AA

AF:

0.105

AC:

462

ESP6500EA

AF:

0.299

AC:

2570

ExAC

AF:

0.236

AC:

28668

Asia WGS

AF:

0.180

AC:

625

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Oct 16, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 30681437) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.065

T;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.79

T;T

MetaRNN

Benign

0.0058

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.

PhyloP100

0.67

PrimateAI

Benign

0.22

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.055

Sift

Benign

0.29

T;T

Sift4G

Benign

0.25

T;T

Polyphen

0.054

B;.

Vest4

0.023

MPC

0.18

ClinPred

0.010

GERP RS

2.8

Varity_R

0.035

gMVP

0.18

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over