chr11-2883974-G-GC

Position:

• chr11-2883974-G-GC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001122630.2(CDKN1C):​c.*5+24_*5+25insG 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.00

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]

ACMG classification

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/exons	MANE	UniProt
CDKN1C	NM_001122630.2	c.*5+24_*5+25insG		intron_variant		ENST00000440480.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKN1C	ENST00000440480.8	c.*5+24_*5+25insG		intron_variant		1	NM_001122630.2	A2

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46062 AN: 151524 Hom.: 7695 Cov.: 0

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

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.: 32 AF XY: 0.334 AC XY: 231464 AN XY: 692560

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.: 0 AF XY: 0.307 AC XY: 22715 AN XY: 74106

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

Submissions by phenotype

CDKN1C-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 26, 2019

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

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

Other links and lift over

dbSNP: rs34289096; hg19: chr11-2905204;