Variant 12-12717002-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.177

Variant links:

Genes affected

GPR19 (HGNC:):

GPR19 links:

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]

CDKN1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	UniProt
GPR19	XM_011520623.4 linkuse as main transcript	c.-1496G>T		5_prime_UTR_variant	1/4

Ensembl

Gene	Transcript	HGVSc	Effect	TSL
CDKN1B	ENST00000477087.1 linkuse as main transcript	n.154+1119C>A	intron_variant, non_coding_transcript_variant	3
CDKN1B	ENST00000682620.1 linkuse as main transcript	n.1631-1823C>A	intron_variant, non_coding_transcript_variant
CDKN1B	ENST00000684771.1 linkuse as main transcript	n.585-1823C>A	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58806

AN:

152010

Hom.:

12127

Cov.:

show subpopulations

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.:

AF XY:

0.436

AC XY:

170019

AN XY:

390116

show subpopulations

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.:

AF XY:

0.390

AC XY:

28992

AN XY:

74386

show subpopulations

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

LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over