rs3759216

Positions:

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

Variant summary

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

The XM_011520623.4(GPR19):​c.-205+559C>T variant causes a intron 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: GPR19 XM_011520623.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.840

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=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR19	XM_011520623.4	c.-205+559C>T		intron_variant			XP_011518925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN1B	ENST00000682080.1	n.2305G>A		non_coding_transcript_exon_variant	3/3
CDKN1B	ENST00000477087.1	n.47+48G>A		intron_variant, non_coding_transcript_variant		3
CDKN1B	ENST00000682620.1	n.1631-3673G>A		intron_variant, non_coding_transcript_variant
CDKN1B	ENST00000684771.1	n.585-3673G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

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

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.375

Alfa AF: 0.439 Hom.: 8677

Bravo AF: 0.373

Asia WGS AF: 0.403 AC: 1400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3759216; hg19: chr12-12868086;