11-2884046-G-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001122630.2(CDKN1C):c.876C>A(p.Gly292=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G292G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDKN1C NM_001122630.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.066343606).
• BP7: Synonymous conserved (PhyloP=-0.323 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKN1C	NM_001122630.2	c.876C>A	p.Gly292=	synonymous_variant	3/4	ENST00000440480.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKN1C	ENST00000440480.8	c.876C>A	p.Gly292=	synonymous_variant	3/4	1	NM_001122630.2	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1402846 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 692846

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
Cadd	Benign	4.0
Dann	Benign	0.82
DEOGEN2	Benign	0.0097	T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.079	N
M_CAP	Pathogenic	0.48	D
MetaRNN	Benign	0.066	T;T
MetaSVM	Benign	-0.76	T
MutationTaster	Benign	1.0	N;N;N;N;N
PROVEAN	Benign	0.78	N;.
REVEL	Benign	0.18
Sift	Benign	0.29	T;.
Sift4G	Benign	0.33	T;.
Polyphen		0.45	B;.
Vest4		0.086
MutPred		0.24		Gain of solvent accessibility (P = 0.0145);Gain of solvent accessibility (P = 0.0145);
MVP		0.40
ClinPred		0.089	T
GERP RS		-5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

Other links and lift over

dbSNP: rs377216794; hg19: chr11-2905276;