rs758244300

Positions:

• chr11-2885417-C-A
• chr11-2885417-C-G
• chr11-2885417-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001122630.2(CDKN1C):​c.40G>T​(p.Val14Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,400,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CDKN1C NM_001122630.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.828

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14744183).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKN1C	NM_001122630.2	c.40G>T	p.Val14Leu	missense_variant	2/4	ENST00000440480.8	NP_001116102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN1C	ENST00000440480.8	c.40G>T	p.Val14Leu	missense_variant	2/4	1	NM_001122630.2	ENSP00000411257.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000129 AC: 2 AN: 155056 Hom.: 0 AF XY: 0.0000120 AC XY: 1 AN XY: 83472

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000321

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1400064 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 691658

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: 0.00000277

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000875 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.062	T;T;.;T;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.80	.;T;T;.;T
M_CAP	Pathogenic	0.53	D
MetaRNN	Benign	0.15	T;T;T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	0.34	N;N;.;.;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.47	N;N;N;N;.
REVEL	Benign	0.12
Sift	Benign	0.039	D;D;D;T;.
Sift4G	Benign	0.081	T;T;T;T;.
Polyphen		0.011	B;B;.;B;.
Vest4		0.048
MutPred		0.25		Loss of MoRF binding (P = 0.0956);Loss of MoRF binding (P = 0.0956);.;.;.;
MVP		0.41
MPC		1.7
ClinPred		0.096	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.19
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs758244300; hg19: chr11-2906647;