14-54398245-C-G

Variant names:

• chr14-54398245-C-G
• rs1884014
• NM_005192.4:c.9+1168C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005192.4(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 NM_005192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.684
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005192.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN3	NM_005192.4	MANE Select	c.9+1168C>G		intron	N/A	NP_005183.2
	CDKN3	NM_001330173.2		c.9+1168C>G		intron	N/A	NP_001317102.1
	CDKN3	NM_001130851.2		c.9+1168C>G		intron	N/A	NP_001124323.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN3	ENST00000335183.11	TSL:1 MANE Select	c.9+1168C>G		intron	N/A	ENSP00000335357.6
	CDKN3	ENST00000442975.6	TSL:1	c.9+1168C>G		intron	N/A	ENSP00000415333.2
	CDKN3	ENST00000929368.1		c.9+1168C>G		intron	N/A	ENSP00000599427.1

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

African (AFR) AF: 0.275 AC: 11429 AN: 41504

American (AMR) AF: 0.234 AC: 3583 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 579 AN: 3470

East Asian (EAS) AF: 0.378 AC: 1962 AN: 5188

South Asian (SAS) AF: 0.337 AC: 1624 AN: 4826

European-Finnish (FIN) AF: 0.163 AC: 1728 AN: 10602

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14649 AN: 68004

Other (OTH) AF: 0.223 AC: 471 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.4
DANN	Benign	0.70
PhyloP100		0.68
Mutation Taster		=100/0	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: rs1884014; hg19: chr14-54864963;