Genetic Variant NM_005288.4:c.-15-105A>G (chr13-26759947-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.-15-105A>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

Publications

0 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=-0.87).

BP6

Variant 13-26759947-T-C is Benign according to our data. Variant chr13-26759947-T-C is described in ClinVar as Benign. ClinVar VariationId 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.

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.-15-105A>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.-15-105A>G	intron	N/A	ENSP00000384932.3	P47775
GPR12	ENST00000381436.2	TSL:6	c.-120A>G	5_prime_UTR	Exon 1 of 1	ENSP00000370844.2	P47775
GPR12	ENST00000881746.1		c.-8-112A>G	intron	N/A	ENSP00000551805.1

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

African (AFR)

AF:

0.0863

AC:

2425

AN:

28102

American (AMR)

AF:

0.0704

AC:

1377

AN:

19572

Ashkenazi Jewish (ASJ)

AF:

0.0670

AC:

1238

AN:

18472

East Asian (EAS)

AF:

0.000114

AC:

AN:

34986

South Asian (SAS)

AF:

0.0235

AC:

1277

AN:

54338

European-Finnish (FIN)

AF:

0.0495

AC:

2202

AN:

44520

Middle Eastern (MID)

AF:

0.0724

AC:

269

AN:

3716

European-Non Finnish (NFE)

AF:

0.101

AC:

102528

AN:

1016320

Other (OTH)

AF:

0.0819

AC:

4315

AN:

52656

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

5200

10400

15599

20799

25999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3896

7792

11688

15584

19480

<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:

0.0831

AC:

12649

AN:

152222

Hom.:

573

Cov.:

AF XY:

0.0781

AC XY:

5810

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0850

AC:

3531

AN:

41538

American (AMR)

AF:

0.0770

AC:

1178

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0698

AC:

242

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.0180

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0437

AC:

463

AN:

10600

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.101

AC:

6838

AN:

68006

Other (OTH)

AF:

0.0962

AC:

203

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

590

1180

1770

2360

2950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<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:

0.0894

Hom.:

353

Bravo

AF:

0.0854

Asia WGS

AF:

0.0210

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

-0.87

CADD

Benign

0.19

(source)

DANN

Benign

0.61

PhyloP100

-2.1

PromoterAI

0.0027

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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