14-54409466-T-C

Variant names:

• chr14-54409466-T-C
• rs4251631
• NM_005192.4:c.193+677T>C

Variant summary

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

The NM_005192.4(CDKN3):​c.193+677T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,044 control chromosomes in the GnomAD database, including 6,924 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 0.28 (6924 hom., cov: 31)
• Consequence: CDKN3 NM_005192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202
• Publications: 11 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=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN3	NM_005192.4	c.193+677T>C		intron_variant	Intron 4 of 7	ENST00000335183.11	NP_005183.2
CDKN3	NM_001330173.2	c.193+677T>C		intron_variant	Intron 4 of 8		NP_001317102.1
CDKN3	NM_001130851.2	c.73+677T>C		intron_variant	Intron 3 of 6		NP_001124323.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN3	ENST00000335183.11	c.193+677T>C		intron_variant	Intron 4 of 7	1	NM_005192.4	ENSP00000335357.6

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43208 AN: 151924 Hom.: 6905 Cov.: 31

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.285 AC: 43276 AN: 152044 Hom.: 6924 Cov.: 31 AF XY: 0.283 AC XY: 21043 AN XY: 74318

African (AFR) AF: 0.420 AC: 17395 AN: 41458

American (AMR) AF: 0.256 AC: 3909 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 588 AN: 3472

East Asian (EAS) AF: 0.368 AC: 1901 AN: 5164

South Asian (SAS) AF: 0.337 AC: 1626 AN: 4824

European-Finnish (FIN) AF: 0.163 AC: 1730 AN: 10584

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15282 AN: 67958

Other (OTH) AF: 0.264 AC: 555 AN: 2104

Alfa AF: 0.244 Hom.: 4779

Bravo AF: 0.295

Asia WGS AF: 0.365 AC: 1266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.5
DANN	Benign	0.83
PhyloP100		-0.20
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: rs4251631; hg19: chr14-54876184;