Variant chr11-2885573-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

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

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 -7 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 id is 236948.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1, Benign=3}. Variant chr11-2885573-C-T is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 898 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKN1C	NM_001122630.2 linkuse as main transcript	c.-11+61G>A		intron_variant		ENST00000440480.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKN1C	ENST00000440480.8 linkuse as main transcript	c.-11+61G>A		intron_variant		1	NM_001122630.2	A2	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

Gnomad4 AFR exome

AF:

0.00155

Gnomad4 AMR exome

AF:

0.00873

Gnomad4 ASJ exome

AF:

0.000375

Gnomad4 EAS exome

AF:

0.0000282

Gnomad4 SAS exome

AF:

0.000654

Gnomad4 FIN exome

AF:

0.00382

Gnomad4 NFE exome

AF:

0.00985

Gnomad4 OTH exome

AF:

0.00783

GnomAD4 genome

AF:

0.00590

AC:

898

AN:

152290

Hom.:

Cov.:

AF XY:

0.00584

AC XY:

435

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.00941

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00283

Gnomad4 NFE

AF:

0.00937

Gnomad4 OTH

AF:

0.00948

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 22, 2022	- -
Benign, criteria provided, single submitter	curation	Sema4, Sema4	Sep 17, 2020	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Feb 27, 2017	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	CDKN1C: BS1, BS2 -

IMAGe syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

Jun 08, 2018

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

DANN

Benign

0.96

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

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