12-12717038-G-T

Position:

• chr12-12717038-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The XM_011520623.4(GPR19):​c.-1532C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 1,004,202 control chromosomes in the GnomAD database, including 338,726 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (43856 hom., cov: 35)
  • Exomes 𝑓: 0.83 (294870 hom.)
• Consequence: GPR19 XM_011520623.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.17

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 12-12717038-G-T is Benign according to our data. Variant chr12-12717038-G-T is described in ClinVar as [Benign]. Clinvar id is 1266363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR19	XM_011520623.4	c.-1532C>A		5_prime_UTR_variant	1/4		XP_011518925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN1B	ENST00000477087.1	n.154+1155G>T		intron_variant, non_coding_transcript_variant		3
CDKN1B	ENST00000682620.1	n.1631-1787G>T		intron_variant, non_coding_transcript_variant
CDKN1B	ENST00000684771.1	n.585-1787G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113667 AN: 152000 Hom.: 43842 Cov.: 35

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.944

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.748

GnomAD4 exome AF: 0.830 AC: 707592 AN: 852092 Hom.: 294870 Cov.: 46 AF XY: 0.830 AC XY: 326604 AN XY: 393572

Gnomad4 AFR exome AF: 0.533

Gnomad4 AMR exome AF: 0.681

Gnomad4 ASJ exome AF: 0.767

Gnomad4 EAS exome AF: 0.930

Gnomad4 SAS exome AF: 0.837

Gnomad4 FIN exome AF: 0.851

Gnomad4 NFE exome AF: 0.837

Gnomad4 OTH exome AF: 0.812

GnomAD4 genome AF: 0.748 AC: 113712 AN: 152110 Hom.: 43856 Cov.: 35 AF XY: 0.748 AC XY: 55647 AN XY: 74376

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.679

Gnomad4 ASJ AF: 0.778

Gnomad4 EAS AF: 0.943

Gnomad4 SAS AF: 0.837

Gnomad4 FIN AF: 0.849

Gnomad4 NFE AF: 0.837

Gnomad4 OTH AF: 0.751

Alfa AF: 0.790 Hom.: 6025

Bravo AF: 0.727

Asia WGS AF: 0.848 AC: 2943 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.66
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs36228498; hg19: chr12-12869972;