14-102348705-C-T

Variant names:

• chr14-102348705-C-T
• rs7011
• NM_032630.3:c.491G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.667
• Publications: 36 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032630.3. 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
	CINP	NM_032630.3	MANE Select	c.491G>A	p.Arg164His	missense	Exon 5 of 5	NP_116019.1	Q9BW66-1
	CINP	NM_001320046.2		c.*4G>A		3_prime_UTR	Exon 4 of 4	NP_001306975.1	Q9BW66-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CINP	ENST00000216756.11	TSL:1 MANE Select	c.491G>A	p.Arg164His	missense	Exon 5 of 5	ENSP00000216756.6	Q9BW66-1
	CINP	ENST00000559504.5	TSL:1	n.491G>A		non_coding_transcript_exon	Exon 4 of 6	ENSP00000453846.1	H0YN33
	CINP	ENST00000536961.6	TSL:3	c.536G>A	p.Arg179His	missense	Exon 5 of 5	ENSP00000442057.2	Q9BW66-3

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32932 AN: 152072 Hom.: 4153 Cov.: 32

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

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.: 42 AF XY: 0.274 AC XY: 198840 AN XY: 726714

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

GnomAD4 genome AF: 0.217 AC: 32960 AN: 152190 Hom.: 4160 Cov.: 32 AF XY: 0.212 AC XY: 15772 AN XY: 74412

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: 85 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20043 AN: 67964

Other (OTH) AF: 0.232 AC: 489 AN: 2112

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.79	T
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.67
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.055
Sift	Benign	0.29	T
Sift4G	Benign	0.25	T
Polyphen		0.054	B
Vest4		0.023
MPC		0.18
ClinPred		0.010	T
GERP RS		2.8
Varity_R		0.035
gMVP		0.18
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7011; hg19: chr14-102815042; COSMIC: COSV53736670; COSMIC: COSV53736670;