rs1884014

Positions:

• chr14-54398245-C-G
• chr14-54398245-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000335183.11(CDKN3):​c.9+1168C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,206 control chromosomes in the GnomAD database, including 4,619 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (4619 hom., cov: 33)
• Consequence: CDKN3 ENST00000335183.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.684

Genes affected

CDKN3 (HGNC:1791): (cyclin dependent kinase inhibitor 3) The protein encoded by this gene belongs to the dual specificity protein phosphatase family. It was identified as a cyclin-dependent kinase inhibitor, and has been shown to interact with, and dephosphorylate CDK2 kinase, thus prevent the activation of CDK2 kinase. This gene was reported to be deleted, mutated, or overexpressed in several kinds of cancers. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKN3	NM_005192.4	c.9+1168C>G		intron_variant		ENST00000335183.11	NP_005183.2
CDKN3	NM_001130851.2	c.9+1168C>G		intron_variant			NP_001124323.1
CDKN3	NM_001330173.2	c.9+1168C>G		intron_variant			NP_001317102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN3	ENST00000335183.11	c.9+1168C>G		intron_variant		1	NM_005192.4	ENSP00000335357	P2

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36274 AN: 152086 Hom.: 4622 Cov.: 33

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.224

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.238 AC: 36300 AN: 152206 Hom.: 4619 Cov.: 33 AF XY: 0.240 AC XY: 17828 AN XY: 74428

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.223

Alfa AF: 0.219 Hom.: 482

Bravo AF: 0.244

Asia WGS AF: 0.350 AC: 1216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.4
DANN	Benign	0.70

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

Other links and lift over

dbSNP: rs1884014; hg19: chr14-54864963;