Variant chr14-102348705-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
CINP	NM_032630.3 linkuse as main transcript	c.491G>A	p.Arg164His	missense_variant	5/5	ENST00000216756.11	NP_116019.1	Q9BW66-1A0A024R6M9
CINP	NM_001320046.2 linkuse as main transcript	c.*4G>A		3_prime_UTR_variant	4/4		NP_001306975.1	Q9BW66-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CINP	ENST00000216756.11 linkuse as main transcript	c.491G>A	p.Arg164His	missense_variant	5/5	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

GnomAD3 exomes

AF:

0.236

AC:

58846

AN:

249500

Hom.:

7702

AF XY:

0.243

AC XY:

32771

AN XY:

134898

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 SAS exome

AF:

0.237

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

Gnomad4 AFR exome

AF:

0.0938

Gnomad4 AMR exome

AF:

0.188

Gnomad4 ASJ exome

AF:

0.352

Gnomad4 EAS exome

AF:

0.108

Gnomad4 SAS exome

AF:

0.236

Gnomad4 FIN exome

AF:

0.181

Gnomad4 NFE exome

AF:

0.295

Gnomad4 OTH exome

AF:

0.269

GnomAD4 genome

AF:

0.217

AC:

32960

AN:

152190

Hom.:

4160

Cov.:

AF XY:

0.212

AC XY:

15772

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.218

Gnomad4 ASJ

AF:

0.353

Gnomad4 EAS

AF:

0.0946

Gnomad4 SAS

AF:

0.232

Gnomad4 FIN

AF:

0.170

Gnomad4 NFE

AF:

0.295

Gnomad4 OTH

AF:

0.232

Alfa

AF:

0.274

Hom.:

11267

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2019	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

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;.

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

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

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