12-12720299-G-C

Position:

• chr12-12720299-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004064.5(CDKN1B):​c.*9-737G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 151,948 control chromosomes in the GnomAD database, including 29,868 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.61 (29868 hom., cov: 32)
• Consequence: CDKN1B NM_004064.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.976

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKN1B	NM_004064.5	c.*9-737G>C		intron_variant		ENST00000228872.9	NP_004055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN1B	ENST00000228872.9	c.*9-737G>C		intron_variant		1	NM_004064.5	ENSP00000228872	P1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93360 AN: 151830 Hom.: 29880 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.621

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.614 AC: 93358 AN: 151948 Hom.: 29868 Cov.: 32 AF XY: 0.613 AC XY: 45520 AN XY: 74250

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.551

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.872

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.690

Gnomad4 OTH AF: 0.618

Alfa AF: 0.655 Hom.: 4109

Bravo AF: 0.599

Asia WGS AF: 0.744 AC: 2588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.66

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: rs34329; hg19: chr12-12873233;