13-26759887-T-C

Variant names:

• chr13-26759887-T-C
• rs76476101
• NM_005288.4:c.-15-45A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.56
• Publications: 2 publications found

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]

ENSG00000299861 (HGNC:):

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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.: 31

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.: 32 AF XY: 0.0673 AC XY: 44693 AN XY: 664526

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: 10 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

GnomAD4 genome AF: 0.0649 AC: 9875 AN: 152084 Hom.: 373 Cov.: 31 AF XY: 0.0648 AC XY: 4815 AN XY: 74338

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: 4 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: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0757 AC: 5148 AN: 67980

Other (OTH) AF: 0.0578 AC: 122 AN: 2110

Alfa AF: 0.0710 Hom.: 100

Bravo AF: 0.0610

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.62
PhyloP100		-1.6
PromoterAI		0.073	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs76476101; hg19: chr13-27334024;