rs3093736

Positions:

• chr12-12720367-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004064.5(CDKN1B):​c.*9-669G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0228 in 152,236 control chromosomes in the GnomAD database, including 59 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 0.023 (59 hom., cov: 32)
• Consequence: CDKN1B NM_004064.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130

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]

CDKN1B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0228 (3466/152236) while in subpopulation NFE AF= 0.0319 (2170/68006). AF 95% confidence interval is 0.0308. There are 59 homozygotes in gnomad4. There are 1729 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3466 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKN1B	NM_004064.5	c.*9-669G>A		intron_variant		ENST00000228872.9	NP_004055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN1B	ENST00000228872.9	c.*9-669G>A		intron_variant		1	NM_004064.5	ENSP00000228872.4

Frequencies

GnomAD3 genomes AF: 0.0228 AC: 3466 AN: 152118 Hom.: 59 Cov.: 32

Gnomad AFR AF: 0.00521

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.00943

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00765

Gnomad FIN AF: 0.0700

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0319

Gnomad OTH AF: 0.0168

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

GnomAD4 genome AF: 0.0228 AC: 3466 AN: 152236 Hom.: 59 Cov.: 32 AF XY: 0.0232 AC XY: 1729 AN XY: 74426

Gnomad4 AFR AF: 0.00520

Gnomad4 AMR AF: 0.00942

Gnomad4 ASJ AF: 0.0291

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00786

Gnomad4 FIN AF: 0.0700

Gnomad4 NFE AF: 0.0319

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0289 Hom.: 32

Bravo AF: 0.0179

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.28

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: rs3093736; hg19: chr12-12873301;