dbSNP rs143992355: CDKN1C:c.-85G>A (chr11-2885574-C-T) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.0310

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 -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 rank	MANE	Protein	UniProt
CDKN1C	NM_001122630.2 link	c.-11+60G>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+60G>A		intron_variant	Intron 1 of 3	1	NM_001122630.2	ENSP00000411257.2		P49918-2

Frequencies

GnomAD3 genomes

AF:

0.0277

AC:

4209

AN:

152122

Hom.:

101

Cov.:

show subpopulations

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.:

AF XY:

0.0378

AC XY:

25066

AN XY:

663422

show subpopulations

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.:

AF XY:

0.0254

AC XY:

1888

AN XY:

74422

show subpopulations

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.:

Bravo

AF:

0.0289

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 27, 2018

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Beckwith-Wiedemann syndrome

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 14, 2020

Sema4, Sema4

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

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