12-12717002-C-A

Position:

• chr12-12717002-C-A

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.-1496G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 996,668 control chromosomes in the GnomAD database, including 93,107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12128 hom., cov: 33)
  • Exomes 𝑓: 0.44 (80979 hom.)
• Consequence: GPR19 XM_011520623.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.177

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:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 12-12717002-C-A is Benign according to our data. Variant chr12-12717002-C-A is described in ClinVar as [Benign]. Clinvar id is 695291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR19	XM_011520623.4	c.-1496G>T		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+1119C>A		intron_variant		3
CDKN1B	ENST00000682620.1	n.1631-1823C>A		intron_variant
CDKN1B	ENST00000684771.1	n.585-1823C>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58806 AN: 152010 Hom.: 12127 Cov.: 33

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.375

GnomAD4 exome AF: 0.437 AC: 368860 AN: 844544 Hom.: 80979 Cov.: 31 AF XY: 0.436 AC XY: 170019 AN XY: 390116

Gnomad4 AFR exome AF: 0.212

Gnomad4 AMR exome AF: 0.392

Gnomad4 ASJ exome AF: 0.447

Gnomad4 EAS exome AF: 0.438

Gnomad4 SAS exome AF: 0.443

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.442

Gnomad4 OTH exome AF: 0.419

GnomAD4 genome AF: 0.387 AC: 58815 AN: 152124 Hom.: 12128 Cov.: 33 AF XY: 0.390 AC XY: 28992 AN XY: 74386

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.373

Alfa AF: 0.434 Hom.: 1869

Bravo AF: 0.373

Asia WGS AF: 0.391 AC: 1356 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Multiple endocrine neoplasia type 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 04, 2020

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

This variant is associated with the following publications: (PMID: 15061869, 19667240) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.7
DANN	Benign	0.90

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs36228499; hg19: chr12-12869936;