7-113084740-G-T

Position:

• chr7-113084740-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001146267.2(GPR85):​c.-19C>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.244 in 1,582,912 control chromosomes in the GnomAD database, including 49,344 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 0.24 (4661 hom., cov: 30)
  • Exomes 𝑓: 0.24 (44683 hom.)
• Consequence: GPR85 NM_001146267.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.57

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR85	NM_001146267.2	c.-19C>A		5_prime_UTR_variant	3/3	ENST00000424100.2	NP_001139739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR85	ENST00000424100.2	c.-19C>A		5_prime_UTR_variant	3/3	1	NM_001146267.2	ENSP00000396763	P1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36506 AN: 151796 Hom.: 4660 Cov.: 30

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.0422

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.272

GnomAD3 exomes AF: 0.234 AC: 54707 AN: 233814 Hom.: 6868 AF XY: 0.240 AC XY: 30357 AN XY: 126324

Gnomad AFR exome AF: 0.225

Gnomad AMR exome AF: 0.180

Gnomad ASJ exome AF: 0.297

Gnomad EAS exome AF: 0.0450

Gnomad SAS exome AF: 0.270

Gnomad FIN exome AF: 0.217

Gnomad NFE exome AF: 0.273

Gnomad OTH exome AF: 0.251

GnomAD4 exome AF: 0.244 AC: 349317 AN: 1431000 Hom.: 44683 Cov.: 30 AF XY: 0.246 AC XY: 174691 AN XY: 711154

Gnomad4 AFR exome AF: 0.231

Gnomad4 AMR exome AF: 0.187

Gnomad4 ASJ exome AF: 0.288

Gnomad4 EAS exome AF: 0.0354

Gnomad4 SAS exome AF: 0.267

Gnomad4 FIN exome AF: 0.219

Gnomad4 NFE exome AF: 0.252

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.240 AC: 36525 AN: 151912 Hom.: 4661 Cov.: 30 AF XY: 0.236 AC XY: 17500 AN XY: 74260

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.0419

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.277

Alfa AF: 0.253 Hom.: 3385

Bravo AF: 0.238

Asia WGS AF: 0.203 AC: 706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.91

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: rs1575012; hg19: chr7-112724795; COSMIC: COSV51783353;