12-12714547-G-C

Variant names:

• chr12-12714547-G-C
• rs11055027
• ENST00000682080.1:n.1700G>C

Variant summary

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

The ENST00000682080.1(CDKN1B):​n.1700G>C 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 0.255 in 152,084 control chromosomes in the GnomAD database, including 5,139 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 0.25 (5139 hom., cov: 32)
• Consequence: CDKN1B ENST00000682080.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.394
• Publications: 2 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN1B	ENST00000682080.1		n.1700G>C		non_coding_transcript_exon	Exon 3 of 3
	CDKN1B	ENST00000682620.1		n.1631-4278G>C		intron	N/A
	CDKN1B	ENST00000684771.1		n.585-4278G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38689 AN: 151966 Hom.: 5132 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.255 AC: 38735 AN: 152084 Hom.: 5139 Cov.: 32 AF XY: 0.254 AC XY: 18884 AN XY: 74366

African (AFR) AF: 0.323 AC: 13392 AN: 41456

American (AMR) AF: 0.191 AC: 2913 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 872 AN: 3470

East Asian (EAS) AF: 0.181 AC: 939 AN: 5182

South Asian (SAS) AF: 0.244 AC: 1175 AN: 4824

European-Finnish (FIN) AF: 0.241 AC: 2546 AN: 10576

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15968 AN: 67992

Other (OTH) AF: 0.252 AC: 531 AN: 2108

Alfa AF: 0.231 Hom.: 521

Bravo AF: 0.254

Asia WGS AF: 0.220 AC: 768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.8
DANN	Benign	0.61
PhyloP100		0.39

Splicing

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

Other links and lift over

dbSNP: rs11055027; hg19: chr12-12867481;