11-2883974-G-GC

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

Beckwith-Wiedemann syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
IMAGe syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Illumina, G2P, Ambry Genetics
rhabdomyosarcoma
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
Beckwith-Wiedemann syndrome due to CDKN1C mutation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
intrauterine growth restriction-short stature-early adult-onset diabetes syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Silver-Russell syndrome
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CDKN1C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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

GnomAD2 exomes

AF:

0.359

AC:

55898

AN:

155866

AF XY:

0.362

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 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

African (AFR)

AF:

0.226

AC:

7277

AN:

32250

American (AMR)

AF:

0.338

AC:

12602

AN:

37330

Ashkenazi Jewish (ASJ)

AF:

0.529

AC:

13329

AN:

25180

East Asian (EAS)

AF:

0.669

AC:

24379

AN:

36418

South Asian (SAS)

AF:

0.405

AC:

32443

AN:

80190

European-Finnish (FIN)

AF:

0.245

AC:

11288

AN:

45988

Middle Eastern (MID)

AF:

0.447

AC:

2527

AN:

5656

European-Non Finnish (NFE)

AF:

0.315

AC:

340694

AN:

1081046

Other (OTH)

AF:

0.361

AC:

20966

AN:

58070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

18213

36425

54638

72850

91063

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.304

AC:

46070

AN:

151640

Hom.:

7691

Cov.:

AF XY:

0.307

AC XY:

22715

AN XY:

74106

show subpopulations

African (AFR)

AF:

0.225

AC:

9334

AN:

41422

American (AMR)

AF:

0.330

AC:

5037

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.547

AC:

1893

AN:

3462

East Asian (EAS)

AF:

0.661

AC:

3360

AN:

5082

South Asian (SAS)

AF:

0.402

AC:

1933

AN:

4808

European-Finnish (FIN)

AF:

0.245

AC:

2572

AN:

10502

Middle Eastern (MID)

AF:

0.479

AC:

140

AN:

292

European-Non Finnish (NFE)

AF:

0.306

AC:

20723

AN:

67790

Other (OTH)

AF:

0.372

AC:

783

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1582

3165

4747

6330

7912

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Sep 17, 2024

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jun 22, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

IMAGe syndrome

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

11-2883974-G-GC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over