rs114598028

Variant names:

• chr6-109979086-C-A
• rs114598028
• NM_005284.5:c.-18-9C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-109979086-C-A
• chr6-109979086-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005284.5(GPR6):​c.-18-9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,408,626 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GPR6 NM_005284.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800
• Publications: 0 publications found

Genes affected

GPR6 (HGNC:4515): (G protein-coupled receptor 6) Predicted to enable sphingosine-1-phosphate 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 positive regulation of cytosolic calcium ion concentration. 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR6	NM_005284.5	c.-18-9C>A		intron_variant	Intron 1 of 1	ENST00000275169.5	NP_005275.1
GPR6	NM_001286099.2	c.28-9C>A		intron_variant	Intron 2 of 2		NP_001273028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR6	ENST00000275169.5	c.-18-9C>A		intron_variant	Intron 1 of 1	6	NM_005284.5	ENSP00000275169.3
GPR6	ENST00000414000.3	c.28-9C>A		intron_variant	Intron 2 of 2	2		ENSP00000406986.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1408626 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 698976

African (AFR) AF: 0.0000318 AC: 1 AN: 31428

American (AMR) AF: 0.00 AC: 0 AN: 36196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23004

East Asian (EAS) AF: 0.00 AC: 0 AN: 39488

South Asian (SAS) AF: 0.00 AC: 0 AN: 79076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39058

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5532

European-Non Finnish (NFE) AF: 9.12e-7 AC: 1 AN: 1096446

Other (OTH) AF: 0.00 AC: 0 AN: 58398

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.1
DANN	Benign	0.89
PhyloP100		0.0080

Splicing

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

Other links and lift over

dbSNP: rs114598028; hg19: chr6-110300289;