rs143992355

Positions:

• chr11-2885574-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_000076.2(CDKN1C):​c.-85G>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 0.0375 in 1,499,538 control chromosomes in the GnomAD database, including 1,287 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (101 hom., cov: 33)
  • Exomes 𝑓: 0.039 (1186 hom.)
• Consequence: CDKN1C NM_000076.2 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0310

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 11-2885574-C-T is Benign according to our data. Variant chr11-2885574-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 254880.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-2885574-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0276 (4205/152238) while in subpopulation NFE AF= 0.0397 (2697/67994). AF 95% confidence interval is 0.0384. There are 101 homozygotes in gnomad4. There are 1888 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4205 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKN1C	NM_001122630.2	c.-11+60G>A		intron_variant		ENST00000440480.8	NP_001116102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN1C	ENST00000440480.8	c.-11+60G>A		intron_variant		1	NM_001122630.2	ENSP00000411257.2

Frequencies

GnomAD3 genomes AF: 0.0277 AC: 4209 AN: 152122 Hom.: 101 Cov.: 33

Gnomad AFR AF: 0.00707

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.0366

Gnomad ASJ AF: 0.0909

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0118

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.0397

Gnomad OTH AF: 0.0388

GnomAD4 exome AF: 0.0386 AC: 52059 AN: 1347300 Hom.: 1186 Cov.: 25 AF XY: 0.0378 AC XY: 25066 AN XY: 663422

Gnomad4 AFR exome AF: 0.00756

Gnomad4 AMR exome AF: 0.0256

Gnomad4 ASJ exome AF: 0.0876

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0101

Gnomad4 FIN exome AF: 0.0153

Gnomad4 NFE exome AF: 0.0429

Gnomad4 OTH exome AF: 0.0383

GnomAD4 genome AF: 0.0276 AC: 4205 AN: 152238 Hom.: 101 Cov.: 33 AF XY: 0.0254 AC XY: 1888 AN XY: 74422

Gnomad4 AFR AF: 0.00703

Gnomad4 AMR AF: 0.0365

Gnomad4 ASJ AF: 0.0909

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0114

Gnomad4 FIN AF: 0.0118

Gnomad4 NFE AF: 0.0397

Gnomad4 OTH AF: 0.0384

Alfa AF: 0.0310 Hom.: 7

Bravo AF: 0.0289

Asia WGS AF: 0.00462 AC: 17 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 27, 2018	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Beckwith-Wiedemann syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 06, 2023	- -
Benign, criteria provided, single submitter	curation	Sema4, Sema4	Jul 14, 2020	- -

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	This variant is associated with the following publications: (PMID: 27884173, 10424811) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
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

Other links and lift over

dbSNP: rs143992355; hg19: chr11-2906804;