Variant chr11-2883974-G-GC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001122630.2(CDKN1C):c.*5+24dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,553,768 control chromosomes in the GnomAD database, including 88,791 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7691 hom., cov: 0)

Exomes 𝑓: 0.33 ( 81100 hom. )

Consequence

CDKN1C
NM_001122630.2 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.00

Variant links:

Genes affected

CDKN1C (HGNC:1786): (cyclin dependent kinase inhibitor 1C) This gene is imprinted, with preferential expression of the maternal allele. The encoded protein is a tight-binding, strong inhibitor of several G1 cyclin/Cdk complexes and a negative regulator of cell proliferation. Mutations in this gene are implicated in sporadic cancers and Beckwith-Wiedemann syndorome, suggesting that this gene is a tumor suppressor candidate. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]

CDKN1C links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 11-2883974-G-GC is Benign according to our data. Variant chr11-2883974-G-GC is described in ClinVar as [Benign]. Clinvar id is 254879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN1C	NM_001122630.2 link	c.*5+24dupG		intron_variant	Intron 3 of 3	ENST00000440480.8	NP_001116102.1	P49918-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN1C	ENST00000440480.8 link	c.5+24_5+25insG		intron_variant	Intron 3 of 3	1	NM_001122630.2	ENSP00000411257.2		P49918-2

Frequencies

GnomAD3 genomes

AF:

0.304

AC:

46062

AN:

151524

Hom.:

7695

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.330

Gnomad ASJ

AF:

0.547

Gnomad EAS

AF:

0.660

Gnomad SAS

AF:

0.404

Gnomad FIN

AF:

0.245

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.306

Gnomad OTH

AF:

0.372

GnomAD3 exomes

AF:

0.359

AC:

55898

AN:

155866

Hom.:

10919

AF XY:

0.362

AC XY:

30890

AN XY:

85418

show subpopulations

Gnomad AFR exome

AF:

0.210

Gnomad AMR exome

AF:

0.342

Gnomad ASJ exome

AF:

0.526

Gnomad EAS exome

AF:

0.659

Gnomad SAS exome

AF:

0.407

Gnomad FIN exome

AF:

0.243

Gnomad NFE exome

AF:

0.310

Gnomad OTH exome

AF:

0.386

GnomAD4 exome

AF:

0.332

AC:

465505

AN:

1402128

Hom.:

81100

Cov.:

AF XY:

0.334

AC XY:

231464

AN XY:

692560

show subpopulations

Gnomad4 AFR exome

AF:

0.226

Gnomad4 AMR exome

AF:

0.338

Gnomad4 ASJ exome

AF:

0.529

Gnomad4 EAS exome

AF:

0.669

Gnomad4 SAS exome

AF:

0.405

Gnomad4 FIN exome

AF:

0.245

Gnomad4 NFE exome

AF:

0.315

Gnomad4 OTH exome

AF:

0.361

GnomAD4 genome

AF:

0.304

AC:

46070

AN:

151640

Hom.:

7691

Cov.:

AF XY:

0.307

AC XY:

22715

AN XY:

74106

show subpopulations

Gnomad4 AFR

AF:

0.225

Gnomad4 AMR

AF:

0.330

Gnomad4 ASJ

AF:

0.547

Gnomad4 EAS

AF:

0.661

Gnomad4 SAS

AF:

0.402

Gnomad4 FIN

AF:

0.245

Gnomad4 NFE

AF:

0.306

Gnomad4 OTH

AF:

0.372

Alfa

AF:

0.245

Hom.:

952

Bravo

AF:

0.312

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

CDKN1C-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 17, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Beckwith-Wiedemann syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

IMAGe syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over