Genetic Variant GPR12:c.-15-105A>G (chr13-26759947-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_005288.4(GPR12):c.-15-105A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.09 in 1,424,904 control chromosomes in the GnomAD database, including 6,295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.083 ( 573 hom., cov: 31)

Exomes 𝑓: 0.091 ( 5722 hom. )

Consequence

GPR12
NM_005288.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.08

Variant links:

Genes affected

GPR12 (HGNC:4466): (G protein-coupled receptor 12) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in adenylate cyclase-activating G protein-coupled receptor signaling pathway and regulation of metabolic process. Predicted to act upstream of or within G protein-coupled receptor signaling pathway and cellular calcium ion homeostasis. Predicted to be integral component of plasma membrane. Predicted to be active in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

GPR12 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 13-26759947-T-C is Benign according to our data. Variant chr13-26759947-T-C is described in ClinVar as [Benign]. Clinvar id is 1291579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR12	NM_005288.4 link	c.-15-105A>G		intron_variant	Intron 1 of 1	ENST00000405846.5	NP_005279.1	P47775A8K2F5
GPR12	XM_005266360.3 link	c.-88-509A>G		intron_variant	Intron 1 of 1		XP_005266417.1	B4DG25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR12	ENST00000405846.5 link	c.-15-105A>G		intron_variant	Intron 1 of 1	1	NM_005288.4	ENSP00000384932.3		P47775
GPR12	ENST00000381436.2 link	c.-120A>G		5_prime_UTR_variant	Exon 1 of 1	6		ENSP00000370844.2		P47775

Frequencies

GnomAD3 genomes

AF:

0.0832

AC:

12648

AN:

152104

Hom.:

574

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0850

Gnomad AMI

AF:

0.0954

Gnomad AMR

AF:

0.0772

Gnomad ASJ

AF:

0.0698

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0184

Gnomad FIN

AF:

0.0437

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.101

Gnomad OTH

AF:

0.0977

GnomAD4 exome

AF:

0.0909

AC:

115635

AN:

1272682

Hom.:

5722

Cov.:

AF XY:

0.0892

AC XY:

54767

AN XY:

614100

show subpopulations

Gnomad4 AFR exome

AF:

0.0863

Gnomad4 AMR exome

AF:

0.0704

Gnomad4 ASJ exome

AF:

0.0670

Gnomad4 EAS exome

AF:

0.000114

Gnomad4 SAS exome

AF:

0.0235

Gnomad4 FIN exome

AF:

0.0495

Gnomad4 NFE exome

AF:

0.101

Gnomad4 OTH exome

AF:

0.0819

GnomAD4 genome

AF:

0.0831

AC:

12649

AN:

152222

Hom.:

573

Cov.:

AF XY:

0.0781

AC XY:

5810

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0850

Gnomad4 AMR

AF:

0.0770

Gnomad4 ASJ

AF:

0.0698

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0180

Gnomad4 FIN

AF:

0.0437

Gnomad4 NFE

AF:

0.101

Gnomad4 OTH

AF:

0.0962

Alfa

AF:

0.0918

Hom.:

229

Bravo

AF:

0.0854

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.19

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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