rs3741341

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001122630.2(CDKN1C):c.675G>A(p.Glu225Glu) 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.

BS2

High AC in GnomAd4 at 339 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN1C	NM_001122630.2 link	c.675G>A	p.Glu225Glu	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.675G>A	p.Glu225Glu	synonymous_variant	Exon 2 of 4	1	NM_001122630.2	ENSP00000411257.2		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

GnomAD2 exomes

AF:

0.00389

AC:

601

AN:

154444

AF XY:

0.00300

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 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

AC:

AN:

27824

Gnomad4 AMR exome

AF:

0.0120

AC:

423

AN:

35186

Gnomad4 ASJ exome

AF:

0.00279

AC:

AN:

22924

Gnomad4 EAS exome

AF:

0.0268

AC:

809

AN:

30238

Gnomad4 SAS exome

AF:

0.00133

AC:

104

AN:

78046

Gnomad4 FIN exome

AF:

0.000488

AC:

AN:

34820

Gnomad4 NFE exome

AF:

0.000205

AC:

217

AN:

1056764

Gnomad4 Remaining exome

AF:

0.00164

AC:

AN:

54366

Heterozygous variant carriers

144

215

287

359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

AC:

0.000435962

AN:

0.000435962

Gnomad4 AMR

AF:

0.00968

AC:

0.00967869

AN:

0.00967869

Gnomad4 ASJ

AF:

0.00318

AC:

0.00317919

AN:

0.00317919

Gnomad4 EAS

AF:

0.0241

AC:

0.0241461

AN:

0.0241461

Gnomad4 SAS

AF:

0.000416

AC:

0.000415628

AN:

0.000415628

Gnomad4 FIN

AF:

0.000396

AC:

0.000396275

AN:

0.000396275

Gnomad4 NFE

AF:

0.000325

AC:

0.00032504

AN:

0.00032504

Gnomad4 OTH

AF:

0.00572

AC:

0.00571973

AN:

0.00571973

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Oct 31, 2013

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Beckwith-Wiedemann syndrome

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.41

CADD

Benign

DANN

Uncertain

0.99

Mutation Taster

=100/0

polymorphism

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