12-12681960-C-A

Position:

• chr12-12681960-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006143.3(GPR19):​c.-23+2391G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,140 control chromosomes in the GnomAD database, including 2,348 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2348 hom., cov: 32)
• Consequence: GPR19 NM_006143.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358

Genes affected

GPR19 (HGNC:4473): (G protein-coupled receptor 19) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in cilium. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000257004 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR19	NM_006143.3	c.-23+2391G>T		intron_variant		ENST00000651487.1	NP_006134.2
GPR19	XM_011520623.4	c.6+2391G>T		intron_variant			XP_011518925.1
GPR19	XM_011520624.3	c.6+2391G>T		intron_variant			XP_011518926.1
GPR19	XM_047428741.1	c.6+2391G>T		intron_variant			XP_047284697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR19	ENST00000651487.1	c.-23+2391G>T		intron_variant			NM_006143.3	ENSP00000498976.1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23769 AN: 152022 Hom.: 2351 Cov.: 32

Gnomad AFR AF: 0.0427

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.179

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.156 AC: 23753 AN: 152140 Hom.: 2348 Cov.: 32 AF XY: 0.152 AC XY: 11309 AN XY: 74378

Gnomad4 AFR AF: 0.0425

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.179

Alfa AF: 0.192 Hom.: 1594

Bravo AF: 0.153

Asia WGS AF: 0.243 AC: 847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.5
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs10845606; hg19: chr12-12834894;