rs2293369

Positions:

• chr7-113080769-C-A
• chr7-113080769-C-G
• chr7-113080769-C-T

Variant summary

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

The ENST00000297146.7(GPR85):​c.*2840G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,806 control chromosomes in the GnomAD database, including 16,975 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 0.46 (16974 hom., cov: 31)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: GPR85 ENST00000297146.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310

Genes affected

GPR85 (HGNC:4536): (G protein-coupled receptor 85) Members of the G protein-coupled receptor (GPCR) family, such as GPR85, have a similar structure characterized by 7 transmembrane domains. Activation of GPCRs by extracellular stimuli, such as neurotransmitters, hormones, or light, induces an intracellular signaling cascade mediated by heterotrimeric GTP-binding proteins, or G proteins (Matsumoto et al., 2000 [PubMed 10833454]).[supplied by OMIM, Aug 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR85	ENST00000297146.7	c.*2840G>T		3_prime_UTR_variant	3/3	1		P1
GPR85	ENST00000610164.1	c.*542-255G>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69840 AN: 151684 Hom.: 16957 Cov.: 31

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.279

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.436

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.460 AC: 69897 AN: 151802 Hom.: 16974 Cov.: 31 AF XY: 0.466 AC XY: 34530 AN XY: 74156

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.917

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.434

Alfa AF: 0.440 Hom.: 14182

Bravo AF: 0.466

Asia WGS AF: 0.585 AC: 2032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2293369; hg19: chr7-112720824;