rs1581688

Positions:

• chr7-113083038-T-C

Variant summary

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

The NM_001146267.2(GPR85):​c.*571A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,566 control chromosomes in the GnomAD database, including 8,478 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 0.33 (8454 hom., cov: 32)
  • Exomes 𝑓: 0.30 (24 hom.)
• Consequence: GPR85 NM_001146267.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.456

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=-0.52).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR85	NM_001146267.2	c.*571A>G		3_prime_UTR_variant	3/3	ENST00000424100.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR85	ENST00000424100.2	c.*571A>G		3_prime_UTR_variant	3/3	1	NM_001146267.2	P1
GPR85	ENST00000297146.7	c.*571A>G		3_prime_UTR_variant	3/3	1		P1
GPR85	ENST00000449591.2	c.*571A>G		3_prime_UTR_variant	2/2	1		P1
GPR85	ENST00000610164.1	c.*541+30A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49619 AN: 151930 Hom.: 8447 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.0577

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.344

GnomAD4 exome AF: 0.297 AC: 154 AN: 518 Hom.: 24 Cov.: 0 AF XY: 0.290 AC XY: 91 AN XY: 314

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.304

Gnomad4 NFE exome AF: 0.276

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.327 AC: 49651 AN: 152048 Hom.: 8454 Cov.: 32 AF XY: 0.321 AC XY: 23884 AN XY: 74312

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.0574

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.348

Alfa AF: 0.363 Hom.: 13612

Bravo AF: 0.319

Asia WGS AF: 0.270 AC: 940 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.8
DANN	Benign	0.70

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: rs1581688; hg19: chr7-112723093;