rs2179896

chr14-54408796-A-Gchr14-54408796-A-T

Variant summary

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

The NM_005192.4(CDKN3):c.193+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 1,568,424 control chromosomes in the GnomAD database, including 395,314 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.71 (37993 hom., cov: 32)
  • Exomes 𝑓: 0.71 (357321 hom.)
• Consequence: CDKN3 NM_005192.4 splice_region, intron
• Scores: Splicing: ADA: 0.00001508
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKN3	NM_005192.4	c.193+7A>G		splice_region_variant, intron_variant		ENST00000335183.11
CDKN3	NM_001130851.2	c.73+7A>G		splice_region_variant, intron_variant
CDKN3	NM_001330173.2	c.193+7A>G		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKN3	ENST00000335183.11	c.193+7A>G		splice_region_variant, intron_variant		1	NM_005192.4	P2

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107422 AN: 151936 Hom.: 37957 Cov.: 32

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.717

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.735

GnomAD3 exomes AF: 0.678 AC: 147772 AN: 218096 Hom.: 50334 AF XY: 0.681 AC XY: 80756 AN XY: 118592

Gnomad AFR exome AF: 0.705

Gnomad AMR exome AF: 0.579

Gnomad ASJ exome AF: 0.713

Gnomad EAS exome AF: 0.641

Gnomad SAS exome AF: 0.645

Gnomad FIN exome AF: 0.650

Gnomad NFE exome AF: 0.713

Gnomad OTH exome AF: 0.679

GnomAD4 exome AF: 0.709 AC: 1004292 AN: 1416370 Hom.: 357321 Cov.: 43 AF XY: 0.709 AC XY: 498713 AN XY: 703162

Gnomad4 AFR exome AF: 0.714

Gnomad4 AMR exome AF: 0.600

Gnomad4 ASJ exome AF: 0.718

Gnomad4 EAS exome AF: 0.678

Gnomad4 SAS exome AF: 0.651

Gnomad4 FIN exome AF: 0.646

Gnomad4 NFE exome AF: 0.721

Gnomad4 OTH exome AF: 0.702

GnomAD4 genome AF: 0.707 AC: 107509 AN: 152054 Hom.: 37993 Cov.: 32 AF XY: 0.701 AC XY: 52121 AN XY: 74324

Gnomad4 AFR AF: 0.718

Gnomad4 AMR AF: 0.683

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.656

Gnomad4 NFE AF: 0.721

Gnomad4 OTH AF: 0.727

Alfa AF: 0.707 Hom.: 25956

Bravo AF: 0.712

Asia WGS AF: 0.644 AC: 2230 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.032
Dann	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000015
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.070		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: rs2179896; hg19: chr14-54875514; COSMIC: COSV53593000;