dbSNP rs529326848: CDKN1C:p.Pro189Pro (chr11-2884890-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001122630.2(CDKN1C):c.567A>G(p.Pro189Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0088 in 741,352 control chromosomes in the GnomAD database, including 206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 162 hom., cov: 31)

Exomes 𝑓: 0.0042 ( 44 hom. )

Consequence

CDKN1C
NM_001122630.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -8.37

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 11-2884890-T-C is Benign according to our data. Variant chr11-2884890-T-C is described in ClinVar as [Benign]. Clinvar id is 236964.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-2884890-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-8.37 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN1C	NM_001122630.2 link	c.567A>G	p.Pro189Pro	synonymous_variant	Exon 2 of 4	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.567A>G	p.Pro189Pro	synonymous_variant	Exon 2 of 4	1	NM_001122630.2	ENSP00000411257.2		P49918-2

Frequencies

GnomAD3 genomes

AF:

0.0360

AC:

3880

AN:

107736

Hom.:

161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.0289

Gnomad AMR

AF:

0.0161

Gnomad ASJ

AF:

0.00465

Gnomad EAS

AF:

0.00111

Gnomad SAS

AF:

0.00924

Gnomad FIN

AF:

0.00135

Gnomad MID

AF:

0.0400

Gnomad NFE

AF:

0.00320

Gnomad OTH

AF:

0.0211

GnomAD4 exome

AF:

0.00416

AC:

2637

AN:

633540

Hom.:

Cov.:

AF XY:

0.00393

AC XY:

1172

AN XY:

298128

show subpopulations

Gnomad4 AFR exome

AF:

0.0897

Gnomad4 AMR exome

AF:

0.00712

Gnomad4 ASJ exome

AF:

0.00385

Gnomad4 EAS exome

AF:

0.00184

Gnomad4 SAS exome

AF:

0.00321

Gnomad4 FIN exome

AF:

0.000664

Gnomad4 NFE exome

AF:

0.00236

Gnomad4 OTH exome

AF:

0.00714

GnomAD4 genome

AF:

0.0361

AC:

3888

AN:

107812

Hom.:

162

Cov.:

AF XY:

0.0345

AC XY:

1829

AN XY:

53056

show subpopulations

Gnomad4 AFR

AF:

0.115

Gnomad4 AMR

AF:

0.0162

Gnomad4 ASJ

AF:

0.00465

Gnomad4 EAS

AF:

0.00112

Gnomad4 SAS

AF:

0.00955

Gnomad4 FIN

AF:

0.00135

Gnomad4 NFE

AF:

0.00320

Gnomad4 OTH

AF:

0.0210

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Aug 17, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 07, 2016

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Beckwith-Wiedemann syndrome

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 24, 2020

Sema4, Sema4

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

not provided

Benign:2

Feb 28, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Beckwith-Wiedemann syndrome;C1846009:IMAGe syndrome

Benign:1

Jan 12, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

7.0

DANN

Benign

0.46

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