rs3759217

Variant names:

• chr12-12715518-C-T
• rs3759217
• ENST00000477087.1:n.48-259C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000477087.1(CDKN1B):​n.48-259C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,196 control chromosomes in the GnomAD database, including 1,369 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 0.12 (1369 hom., cov: 32)
• Consequence: CDKN1B ENST00000477087.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153
• Publications: 22 publications found

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]

GPR19 (HGNC:4473): (G protein-coupled receptor 19) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in cilium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR19	XM_011520623.4	c.-205+193G>A		intron_variant	Intron 1 of 3		XP_011518925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN1B	ENST00000477087.1	n.48-259C>T		intron_variant	Intron 1 of 3	3
CDKN1B	ENST00000682620.1	n.1631-3307C>T		intron_variant	Intron 2 of 3
CDKN1B	ENST00000684771.1	n.585-3307C>T		intron_variant	Intron 2 of 3
CDKN1B	ENST00000682080.1	n.*206C>T		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17971 AN: 152078 Hom.: 1358 Cov.: 32

Gnomad AFR AF: 0.0768

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0416

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.118 AC: 18008 AN: 152196 Hom.: 1369 Cov.: 32 AF XY: 0.122 AC XY: 9078 AN XY: 74380

African (AFR) AF: 0.0772 AC: 3205 AN: 41522

American (AMR) AF: 0.235 AC: 3594 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 503 AN: 3470

East Asian (EAS) AF: 0.0421 AC: 218 AN: 5184

South Asian (SAS) AF: 0.117 AC: 564 AN: 4822

European-Finnish (FIN) AF: 0.134 AC: 1415 AN: 10588

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8002 AN: 68012

Other (OTH) AF: 0.133 AC: 281 AN: 2112

Alfa AF: 0.119 Hom.: 2373

Bravo AF: 0.124

Asia WGS AF: 0.101 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.1
DANN	Benign	0.49
PhyloP100		-0.15

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3759217; hg19: chr12-12868452;