rs188494894

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2

The ENST00000414822.8(CDKN1C):c.-84G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00818 in 1,504,334 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0059 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0084 ( 74 hom. )

Consequence

CDKN1C
ENST00000414822.8 5_prime_UTR

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 0.885

Publications

2 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 11-2885573-C-T is Benign according to our data. Variant chr11-2885573-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 236948.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0059 (898/152290) while in subpopulation AMR AF = 0.00941 (144/15300). AF 95% confidence interval is 0.00876. There are 4 homozygotes in GnomAd4. There are 435 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 898 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN1C	NM_001122630.2 link	c.-11+61G>A		intron_variant	Intron 1 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.-11+61G>A		intron_variant	Intron 1 of 3	1	NM_001122630.2	ENSP00000411257.2		P49918-2

Frequencies

GnomAD3 genomes

AF:

0.00590

AC:

898

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00942

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00283

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00936

Gnomad OTH

AF:

0.00958

GnomAD4 exome

AF:

0.00844

AC:

11406

AN:

1352044

Hom.:

Cov.:

AF XY:

0.00809

AC XY:

5388

AN XY:

665660

show subpopulations

African (AFR)

AF:

0.00155

AC:

AN:

30964

American (AMR)

AF:

0.00873

AC:

302

AN:

34596

Ashkenazi Jewish (ASJ)

AF:

0.000375

AC:

AN:

23996

East Asian (EAS)

AF:

0.0000282

AC:

AN:

35468

South Asian (SAS)

AF:

0.000654

AC:

AN:

76398

European-Finnish (FIN)

AF:

0.00382

AC:

126

AN:

32994

Middle Eastern (MID)

AF:

0.00376

AC:

AN:

4522

European-Non Finnish (NFE)

AF:

0.00985

AC:

10410

AN:

1056546

Other (OTH)

AF:

0.00783

AC:

443

AN:

56560

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

575

1150

1726

2301

2876

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

414

828

1242

1656

2070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00590

AC:

898

AN:

152290

Hom.:

Cov.:

AF XY:

0.00584

AC XY:

435

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00142

AC:

AN:

41582

American (AMR)

AF:

0.00941

AC:

144

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00104

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00283

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00937

AC:

637

AN:

68018

Other (OTH)

AF:

0.00948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

134

178

223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00783

Hom.:

Bravo

AF:

0.00681

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Beckwith-Wiedemann syndrome

Benign:2

Sep 17, 2020

Sema4, Sema4

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

- -

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CDKN1C: BS1, BS2 -

Feb 27, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

IMAGe syndrome

Uncertain:1

Jun 08, 2018

Baylor Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

0.89

PromoterAI

-0.037

Neutral

(source)

Mutation Taster

=298/2

polymorphism

(source)

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

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.

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