11-2883974-G-GCC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001122630.2(CDKN1C):c.*5+24_*5+25insGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0037 in 1,553,992 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0038 (10 hom.)
• Consequence: CDKN1C NM_001122630.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 11-2883974-G-GCC is Benign according to our data. Variant chr11-2883974-G-GCC is described in ClinVar as [Likely_benign]. Clinvar id is 2641505.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 438 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00289 AC: 438 AN: 151584 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000992

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00492

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000392

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00562

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00355

Gnomad OTH AF: 0.00288

GnomAD3 exomes AF: 0.00287 AC: 448 AN: 155866 Hom.: 0 AF XY: 0.00279 AC XY: 238 AN XY: 85418

Gnomad AFR exome AF: 0.000650

Gnomad AMR exome AF: 0.00356

Gnomad ASJ exome AF: 0.00336

Gnomad EAS exome AF: 0.000695

Gnomad SAS exome AF: 0.00115

Gnomad FIN exome AF: 0.00469

Gnomad NFE exome AF: 0.00358

Gnomad OTH exome AF: 0.00138

GnomAD4 exome AF: 0.00378 AC: 5306 AN: 1402292 Hom.: 10 Cov.: 32 AF XY: 0.00372 AC XY: 2578 AN XY: 692672

Gnomad4 AFR exome AF: 0.000868

Gnomad4 AMR exome AF: 0.00348

Gnomad4 ASJ exome AF: 0.00330

Gnomad4 EAS exome AF: 0.000494

Gnomad4 SAS exome AF: 0.00128

Gnomad4 FIN exome AF: 0.00472

Gnomad4 NFE exome AF: 0.00423

Gnomad4 OTH exome AF: 0.00248

GnomAD4 genome AF: 0.00288 AC: 437 AN: 151700 Hom.: 0 Cov.: 0 AF XY: 0.00298 AC XY: 221 AN XY: 74142

Gnomad4 AFR AF: 0.000989

Gnomad4 AMR AF: 0.00484

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.000393

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00562

Gnomad4 NFE AF: 0.00355

Gnomad4 OTH AF: 0.00285

Alfa AF: 0.00169 Hom.: 952

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

CDKN1C: BS1 -

Computational scores

Source: dbNSFP v4.3

Splicing

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;