12-12714547-G-C

Position:

• chr12-12714547-G-C

Variant summary

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

The XM_011520623.4(GPR19):​c.-205+1164C>G variant causes a intron 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: GPR19 XM_011520623.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.394

Genes affected

GPR19 (HGNC:):

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR19	XM_011520623.4	c.-205+1164C>G		intron_variant			XP_011518925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN1B	ENST00000682080.1	n.1700G>C		non_coding_transcript_exon_variant	3/3
CDKN1B	ENST00000682620.1	n.1631-4278G>C		intron_variant, non_coding_transcript_variant
CDKN1B	ENST00000684771.1	n.585-4278G>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.252

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 v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11055027; hg19: chr12-12867481;