Variant chr11-2884782-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001122630.2(CDKN1C):c.675G>A(p.Glu225=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,496,048 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 10 hom. )

Consequence

CDKN1C
NM_001122630.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.612

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 11-2884782-C-T is Benign according to our data. Variant chr11-2884782-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 158190.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-2884782-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.612 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00225 (339/150912) while in subpopulation EAS AF= 0.0241 (123/5094). AF 95% confidence interval is 0.0207. There are 4 homozygotes in gnomad4. There are 188 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 339 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKN1C	NM_001122630.2 linkuse as main transcript	c.675G>A	p.Glu225=	synonymous_variant	2/4	ENST00000440480.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKN1C	ENST00000440480.8 linkuse as main transcript	c.675G>A	p.Glu225=	synonymous_variant	2/4	1	NM_001122630.2	A2	P49918-2

Frequencies

GnomAD3 genomes

AF:

0.00223

AC:

337

AN:

150808

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000437

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00956

Gnomad ASJ

AF:

0.00318

Gnomad EAS

AF:

0.0241

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000396

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000325

Gnomad OTH

AF:

0.00578

GnomAD3 exomes

AF:

0.00389

AC:

601

AN:

154444

Hom.:

AF XY:

0.00300

AC XY:

266

AN XY:

88698

show subpopulations

Gnomad AFR exome

AF:

0.000477

Gnomad AMR exome

AF:

0.0130

Gnomad ASJ exome

AF:

0.00193

Gnomad EAS exome

AF:

0.0212

Gnomad SAS exome

AF:

0.00127

Gnomad FIN exome

AF:

0.000237

Gnomad NFE exome

AF:

0.000369

Gnomad OTH exome

AF:

0.00193

GnomAD4 exome

AF:

0.00129

AC:

1736

AN:

1345136

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

833

AN XY:

668542

show subpopulations

Gnomad4 AFR exome

AF:

0.000252

Gnomad4 AMR exome

AF:

0.0120

Gnomad4 ASJ exome

AF:

0.00279

Gnomad4 EAS exome

AF:

0.0268

Gnomad4 SAS exome

AF:

0.00133

Gnomad4 FIN exome

AF:

0.000488

Gnomad4 NFE exome

AF:

0.000205

Gnomad4 OTH exome

AF:

0.00164

GnomAD4 genome

AF:

0.00225

AC:

339

AN:

150912

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

188

AN XY:

73784

show subpopulations

Gnomad4 AFR

AF:

0.000436

Gnomad4 AMR

AF:

0.00968

Gnomad4 ASJ

AF:

0.00318

Gnomad4 EAS

AF:

0.0241

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.000396

Gnomad4 NFE

AF:

0.000325

Gnomad4 OTH

AF:

0.00572

Alfa

AF:

0.000763

Hom.:

Bravo

AF:

0.00307

Asia WGS

AF:

0.0120

AC:

AN:

3404

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Oct 31, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Beckwith-Wiedemann syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

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