rs384713

Variant names:

• chr11-2884929-A-G
• rs384713
• NM_001122630.2:c.528T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-2884929-A-G
• chr11-2884929-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001122630.2(CDKN1C):​c.528T>C​(p.Ala176Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A176A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000032 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000032 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDKN1C NM_001122630.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.280
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• Beckwith-Wiedemann syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• IMAGe syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Illumina, G2P, Ambry Genetics
• rhabdomyosarcoma

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• Beckwith-Wiedemann syndrome due to CDKN1C mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• intrauterine growth restriction-short stature-early adult-onset diabetes syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Silver-Russell syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-2884929-A-G is Benign according to our data. Variant chr11-2884929-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 454013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.28 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN1C	NM_001122630.2	c.528T>C	p.Ala176Ala	synonymous_variant	Exon 2 of 4	ENST00000440480.8	NP_001116102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN1C	ENST00000440480.8	c.528T>C	p.Ala176Ala	synonymous_variant	Exon 2 of 4	1	NM_001122630.2	ENSP00000411257.2

Frequencies

GnomAD3 genomes AF: 0.0000323 AC: 4 AN: 124008 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000763

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000171

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000325 AC: 24 AN: 739560 Hom.: 0 Cov.: 11 AF XY: 0.0000285 AC XY: 10 AN XY: 350366

African (AFR) AF: 0.00 AC: 0 AN: 13172

American (AMR) AF: 0.00 AC: 0 AN: 4142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7754

East Asian (EAS) AF: 0.00 AC: 0 AN: 11362

South Asian (SAS) AF: 0.000140 AC: 2 AN: 14322

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1804

European-Non Finnish (NFE) AF: 0.0000324 AC: 21 AN: 647464

Other (OTH) AF: 0.0000363 AC: 1 AN: 27586

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000322 AC: 4 AN: 124090 Hom.: 0 Cov.: 32 AF XY: 0.0000661 AC XY: 4 AN XY: 60548

African (AFR) AF: 0.00 AC: 0 AN: 31248

American (AMR) AF: 0.00 AC: 0 AN: 13236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3090

East Asian (EAS) AF: 0.00 AC: 0 AN: 4262

South Asian (SAS) AF: 0.000767 AC: 3 AN: 3912

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.0000171 AC: 1 AN: 58620

Other (OTH) AF: 0.00 AC: 0 AN: 1736

Alfa AF: 0.00388 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Beckwith-Wiedemann syndrome Benign:1

Oct 13, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.2
DANN	Benign	0.20
PhyloP100		-0.28
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

Other links and lift over

dbSNP: rs384713; hg19: chr11-2906159;