rs377573215

Positions:

• chr12-12718226-T-A
• chr12-12718226-T-C

Variant summary

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

The NM_004064.5(CDKN1B):​c.387T>A​(p.His129Gln) variant causes a missense 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H129R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDKN1B NM_004064.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253

Genes affected

CDKN1B (HGNC:1785): (cyclin dependent kinase inhibitor 1B) This gene encodes a cyclin-dependent kinase inhibitor, which shares a limited similarity with CDK inhibitor CDKN1A/p21. The encoded protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes, and thus controls the cell cycle progression at G1. The degradation of this protein, which is triggered by its CDK dependent phosphorylation and subsequent ubiquitination by SCF complexes, is required for the cellular transition from quiescence to the proliferative state. Mutations in this gene are associated with multiple endocrine neoplasia type IV (MEN4). [provided by RefSeq, Apr 2014]

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=0.21891546).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKN1B	NM_004064.5	c.387T>A	p.His129Gln	missense_variant	1/3	ENST00000228872.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKN1B	ENST00000228872.9	c.387T>A	p.His129Gln	missense_variant	1/3	1	NM_004064.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.33	T;T
Eigen	Benign	-0.85
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.29	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.0	N;N
REVEL	Uncertain	0.36
Sift	Benign	0.097	T;T
Sift4G	Benign	0.51	T;T
Polyphen		1.0	D;.
Vest4		0.38
MutPred		0.16		Gain of relative solvent accessibility (P = 0.1066);Gain of relative solvent accessibility (P = 0.1066);
MVP		0.76
MPC		0.29
ClinPred		0.68	D
GERP RS		-7.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.080
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-12871160;