rs2179896

Variant names:

• chr14-54408796-A-G
• rs2179896
• NM_005192.4:c.193+7A>G

Your query was ambiguous. Multiple possible variants found:

• chr14-54408796-A-G
• chr14-54408796-A-T

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+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. 3/3 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
• Publications: 15 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=-0.95).
• 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 rank	MANE	Protein	UniProt
CDKN3	NM_005192.4	c.193+7A>G		splice_region_variant, intron_variant	Intron 4 of 7	ENST00000335183.11	NP_005183.2
CDKN3	NM_001330173.2	c.193+7A>G		splice_region_variant, intron_variant	Intron 4 of 8		NP_001317102.1
CDKN3	NM_001130851.2	c.73+7A>G		splice_region_variant, 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+7A>G		splice_region_variant, intron_variant	Intron 4 of 7	1	NM_005192.4	ENSP00000335357.6

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

GnomAD2 exomes AF: 0.678 AC: 147772 AN: 218096 AF XY: 0.681

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 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

African (AFR) AF: 0.714 AC: 22059 AN: 30884

American (AMR) AF: 0.600 AC: 21099 AN: 35172

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 17994 AN: 25060

East Asian (EAS) AF: 0.678 AC: 25730 AN: 37952

South Asian (SAS) AF: 0.651 AC: 49442 AN: 75938

European-Finnish (FIN) AF: 0.646 AC: 34161 AN: 52842

Middle Eastern (MID) AF: 0.748 AC: 4191 AN: 5606

European-Non Finnish (NFE) AF: 0.721 AC: 788572 AN: 1094454

Other (OTH) AF: 0.702 AC: 41044 AN: 58462

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

African (AFR) AF: 0.718 AC: 29781 AN: 41482

American (AMR) AF: 0.683 AC: 10441 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2477 AN: 3472

East Asian (EAS) AF: 0.669 AC: 3463 AN: 5178

South Asian (SAS) AF: 0.640 AC: 3085 AN: 4818

European-Finnish (FIN) AF: 0.656 AC: 6909 AN: 10540

Middle Eastern (MID) AF: 0.695 AC: 203 AN: 292

European-Non Finnish (NFE) AF: 0.721 AC: 49002 AN: 67966

Other (OTH) AF: 0.727 AC: 1535 AN: 2110

Alfa AF: 0.709 Hom.: 27984

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
PhyloP100		-2.5
PromoterAI		0.0041	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2179896; hg19: chr14-54875514; COSMIC: COSV53593000;