rs3759216

Variant names:

• chr12-12715152-G-A
• rs3759216
• XM_011520623.4:c.-205+559C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-12715152-G-A
• chr12-12715152-G-C
• chr12-12715152-G-T

Variant summary

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

The ENST00000682080.1(CDKN1B):​n.2305G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,116 control chromosomes in the GnomAD database, including 12,103 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 0.39 (12103 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: CDKN1B ENST00000682080.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.840
• Publications: 22 publications found

Genes affected

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]

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 Gene-Disease associations (from GenCC):

• multiple endocrine neoplasia type 4

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
• multiple endocrine neoplasia

  Inheritance: AD Classification: STRONG Submitted by: G2P
• hereditary nonpolyposis colon cancer

  Inheritance: Unknown Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000682080.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN1B	ENST00000682080.1		n.2305G>A		non_coding_transcript_exon	Exon 3 of 3
	CDKN1B	ENST00000477087.1	TSL:3	n.47+48G>A		intron	N/A
	CDKN1B	ENST00000682620.1		n.1631-3673G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58777 AN: 151992 Hom.: 12104 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.377

GnomAD4 exome AF: 0.500 AC: 3 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.386 AC: 58783 AN: 152110 Hom.: 12103 Cov.: 32 AF XY: 0.390 AC XY: 29025 AN XY: 74382

African (AFR) AF: 0.235 AC: 9740 AN: 41482

American (AMR) AF: 0.381 AC: 5824 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1636 AN: 3466

East Asian (EAS) AF: 0.438 AC: 2267 AN: 5176

South Asian (SAS) AF: 0.449 AC: 2166 AN: 4826

European-Finnish (FIN) AF: 0.505 AC: 5334 AN: 10570

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30598 AN: 67990

Other (OTH) AF: 0.375 AC: 792 AN: 2112

Alfa AF: 0.423 Hom.: 13020

Bravo AF: 0.373

Asia WGS AF: 0.403 AC: 1400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.80
PhyloP100		0.84

Splicing

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

Other links and lift over

dbSNP: rs3759216; hg19: chr12-12868086;