Genetic Variant GPR12:c.-15-45A>G (chr13-26759887-T-C) – 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 NM_005288.4(GPR12):c.-15-45A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0677 in 1,511,474 control chromosomes in the GnomAD database, including 3,892 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.065 ( 373 hom., cov: 31)

Exomes 𝑓: 0.068 ( 3519 hom. )

Consequence

GPR12
NM_005288.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.56

Publications

2 publications found

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:

ENSG00000299861 (HGNC:):

ENSG00000299861 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=-0.85).

BP6

Variant 13-26759887-T-C is Benign according to our data. Variant chr13-26759887-T-C is described in ClinVar as Benign. ClinVar VariationId is 1279212.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.074 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005288.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR12	NM_005288.4	MANE Select	c.-15-45A>G		intron	N/A	NP_005279.1	P47775

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GPR12	ENST00000405846.5	TSL:1 MANE Select	c.-15-45A>G	intron	N/A	ENSP00000384932.3	P47775
GPR12	ENST00000381436.2	TSL:6	c.-60A>G	5_prime_UTR	Exon 1 of 1	ENSP00000370844.2	P47775
GPR12	ENST00000881746.1		c.-8-52A>G	intron	N/A	ENSP00000551805.1

Frequencies

GnomAD3 genomes

AF:

0.0649

AC:

9861

AN:

151964

Hom.:

372

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0563

Gnomad AMI

AF:

0.190

Gnomad AMR

AF:

0.0528

Gnomad ASJ

AF:

0.0484

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.0260

Gnomad FIN

AF:

0.0919

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0757

Gnomad OTH

AF:

0.0584

GnomAD4 exome

AF:

0.0680

AC:

92506

AN:

1359390

Hom.:

3519

Cov.:

AF XY:

0.0673

AC XY:

44693

AN XY:

664526

show subpopulations

African (AFR)

AF:

0.0541

AC:

1635

AN:

30202

American (AMR)

AF:

0.0324

AC:

944

AN:

29136

Ashkenazi Jewish (ASJ)

AF:

0.0405

AC:

811

AN:

20046

East Asian (EAS)

AF:

0.000259

AC:

AN:

38670

South Asian (SAS)

AF:

0.0290

AC:

2003

AN:

69078

European-Finnish (FIN)

AF:

0.0985

AC:

4818

AN:

48894

Middle Eastern (MID)

AF:

0.0511

AC:

260

AN:

5092

European-Non Finnish (NFE)

AF:

0.0740

AC:

78655

AN:

1062296

Other (OTH)

AF:

0.0602

AC:

3370

AN:

55976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

3948

7896

11843

15791

19739

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2854

5708

8562

11416

14270

<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:

0.0649

AC:

9875

AN:

152084

Hom.:

373

Cov.:

AF XY:

0.0648

AC XY:

4815

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.0565

AC:

2344

AN:

41496

American (AMR)

AF:

0.0527

AC:

805

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0484

AC:

168

AN:

3470

East Asian (EAS)

AF:

0.000774

AC:

AN:

5168

South Asian (SAS)

AF:

0.0263

AC:

126

AN:

4798

European-Finnish (FIN)

AF:

0.0919

AC:

973

AN:

10588

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0757

AC:

5148

AN:

67980

Other (OTH)

AF:

0.0578

AC:

122

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

473

946

1418

1891

2364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0710

Hom.:

100

Bravo

AF:

0.0610

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.3

(source)

DANN

Benign

0.62

PhyloP100

-1.6

PromoterAI

0.073

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over