dbSNP rs36228499: GPR19:c.-1496G>T (chr12-12717002-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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: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]

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GPR19	XM_011520623.4 link	c.-1496G>T		5_prime_UTR_variant	Exon 1 of 4		XP_011518925.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CDKN1B	ENST00000477087.1 link	n.154+1119C>A	intron_variant	Intron 2 of 3	3
CDKN1B	ENST00000682620.1 link	n.1631-1823C>A	intron_variant	Intron 2 of 3
CDKN1B	ENST00000684771.1 link	n.585-1823C>A	intron_variant	Intron 2 of 3

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

African (AFR)

AF:

0.212

AC:

3424

AN:

16142

American (AMR)

AF:

0.392

AC:

478

AN:

1218

Ashkenazi Jewish (ASJ)

AF:

0.447

AC:

2645

AN:

5922

East Asian (EAS)

AF:

0.438

AC:

2726

AN:

6222

South Asian (SAS)

AF:

0.443

AC:

7335

AN:

16562

European-Finnish (FIN)

AF:

0.500

AC:

142

AN:

284

Middle Eastern (MID)

AF:

0.403

AC:

686

AN:

1702

European-Non Finnish (NFE)

AF:

0.442

AC:

339605

AN:

768312

Other (OTH)

AF:

0.419

AC:

11819

AN:

28180

Heterozygous variant carriers

12750

25499

38249

50998

63748

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

13914

27828

41742

55656

69570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.387

AC:

58815

AN:

152124

Hom.:

12128

Cov.:

AF XY:

0.390

AC XY:

28992

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.234

AC:

9712

AN:

41528

American (AMR)

AF:

0.380

AC:

5811

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.473

AC:

1642

AN:

3472

East Asian (EAS)

AF:

0.438

AC:

2260

AN:

5160

South Asian (SAS)

AF:

0.429

AC:

2071

AN:

4826

European-Finnish (FIN)

AF:

0.505

AC:

5352

AN:

10598

Middle Eastern (MID)

AF:

0.353

AC:

103

AN:

292

European-Non Finnish (NFE)

AF:

0.453

AC:

30747

AN:

67926

Other (OTH)

AF:

0.373

AC:

787

AN:

2108

Heterozygous variant carriers

1821

3643

5464

7286

9107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

578

1156

1734

2312

2890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jan 10, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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