Variant chr11-2884935-AGCCGGGGCCGGGGCCGGG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001122630.2(CDKN1C):c.504_521delCCCGGCCCCGGCCCCGGC(p.Pro169_Ala174del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000307 in 901,018 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

CDKN1C
NM_001122630.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.666

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 -10 ACMG points.

BP6

Variant 11-2884935-AGCCGGGGCCGGGGCCGGG-A is Benign according to our data. Variant chr11-2884935-AGCCGGGGCCGGGGCCGGG-A is described in ClinVar as [Likely_benign]. Clinvar id is 412854.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000236 (32/135466) while in subpopulation NFE AF= 0.000356 (22/61714). AF 95% confidence interval is 0.000241. There are 0 homozygotes in gnomad4. There are 14 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 32 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKN1C	NM_001122630.2 link	c.504_521delCCCGGCCCCGGCCCCGGC	p.Pro169_Ala174del	disruptive_inframe_deletion	2/4	ENST00000440480.8	NP_001116102.1	P49918-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN1C	ENST00000440480.8 link	c.504_521delCCCGGCCCCGGCCCCGGC	p.Pro169_Ala174del	disruptive_inframe_deletion	2/4	1	NM_001122630.2	ENSP00000411257.2		P49918-2

Frequencies

GnomAD3 genomes

AF:

0.000236

AC:

AN:

135376

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000539

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000286

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000516

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000356

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000320

AC:

245

AN:

765552

Hom.:

AF XY:

0.000325

AC XY:

118

AN XY:

362948

show subpopulations

Gnomad4 AFR exome

AF:

0.000137

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000687

Gnomad4 NFE exome

AF:

0.000343

Gnomad4 OTH exome

AF:

0.000174

GnomAD4 genome

AF:

0.000236

AC:

AN:

135466

Hom.:

Cov.:

AF XY:

0.000213

AC XY:

AN XY:

65860

show subpopulations

Gnomad4 AFR

AF:

0.0000537

Gnomad4 AMR

AF:

0.000286

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000516

Gnomad4 NFE

AF:

0.000356

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000650

Hom.:

Bravo

AF:

0.000204

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CDKN1C-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 22, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Beckwith-Wiedemann syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 23, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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