Genetic Variant GPR12:c.*124T>C (chr13-26758699-A-G) – 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.*124T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 1,347,154 control chromosomes in the GnomAD database, including 516,939 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.88 ( 59606 hom., cov: 31)

Exomes 𝑓: 0.87 ( 457333 hom. )

Consequence

GPR12
NM_005288.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.335

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:

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=-0.85).

BP6

Variant 13-26758699-A-G is Benign according to our data. Variant chr13-26758699-A-G is described in ClinVar as [Benign]. Clinvar id is 1226768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR12	NM_005288.4 link	c.*124T>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000405846.5	NP_005279.1	P47775A8K2F5
GPR12	XM_005266360.3 link	c.*124T>C		3_prime_UTR_variant	Exon 2 of 2		XP_005266417.1	B4DG25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR12	ENST00000405846.5 link	c.*124T>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_005288.4	ENSP00000384932.3		P47775
GPR12	ENST00000381436.2 link	c.*124T>C		3_prime_UTR_variant	Exon 1 of 1	6		ENSP00000370844.2		P47775

Frequencies

GnomAD3 genomes

AF:

0.885

AC:

134570

AN:

152074

Hom.:

59574

Cov.:

show subpopulations

Gnomad AFR

AF:

0.886

Gnomad AMI

AF:

0.759

Gnomad AMR

AF:

0.929

Gnomad ASJ

AF:

0.928

Gnomad EAS

AF:

0.984

Gnomad SAS

AF:

0.966

Gnomad FIN

AF:

0.850

Gnomad MID

AF:

0.956

Gnomad NFE

AF:

0.865

Gnomad OTH

AF:

0.904

GnomAD4 exome

AF:

0.874

AC:

1044348

AN:

1194962

Hom.:

457333

Cov.:

AF XY:

0.877

AC XY:

511589

AN XY:

583362

show subpopulations

Gnomad4 AFR exome

AF:

0.891

Gnomad4 AMR exome

AF:

0.944

Gnomad4 ASJ exome

AF:

0.917

Gnomad4 EAS exome

AF:

0.978

Gnomad4 SAS exome

AF:

0.965

Gnomad4 FIN exome

AF:

0.856

Gnomad4 NFE exome

AF:

0.861

Gnomad4 OTH exome

AF:

0.890

GnomAD4 genome

AF:

0.885

AC:

134651

AN:

152192

Hom.:

59606

Cov.:

AF XY:

0.887

AC XY:

65983

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.885

Gnomad4 AMR

AF:

0.929

Gnomad4 ASJ

AF:

0.928

Gnomad4 EAS

AF:

0.984

Gnomad4 SAS

AF:

0.966

Gnomad4 FIN

AF:

0.850

Gnomad4 NFE

AF:

0.865

Gnomad4 OTH

AF:

0.905

Alfa

AF:

0.881

Hom.:

70080

Bravo

AF:

0.892

Asia WGS

AF:

0.949

AC:

3299

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

- -

Nov 12, 2018

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

-0.85

CADD

Benign

2.4

DANN

Benign

0.62

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