NM_001146267.2:c.252T>C

Variant names:

• chr7-113084470-A-G
• rs1608890
• NM_001146267.2:c.252T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001146267.2(GPR85):​c.252T>C​(p.Gly84Gly) variant causes a synonymous change. The variant allele was found at a frequency of 0.885 in 1,613,626 control chromosomes in the GnomAD database, including 633,212 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 0.89 (60113 hom., cov: 31)
  • Exomes 𝑓: 0.89 (573099 hom.)
• Consequence: GPR85 NM_001146267.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.73
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146267.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR85	NM_001146267.2	MANE Select	c.252T>C	p.Gly84Gly	synonymous	Exon 3 of 3	NP_001139739.1
	GPR85	NM_001146265.2		c.252T>C	p.Gly84Gly	synonymous	Exon 3 of 3	NP_001139737.1
	GPR85	NM_001146266.2		c.252T>C	p.Gly84Gly	synonymous	Exon 2 of 2	NP_001139738.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR85	ENST00000424100.2	TSL:1 MANE Select	c.252T>C	p.Gly84Gly	synonymous	Exon 3 of 3	ENSP00000396763.1
	GPR85	ENST00000297146.7	TSL:1	c.252T>C	p.Gly84Gly	synonymous	Exon 3 of 3	ENSP00000297146.2
	GPR85	ENST00000449591.2	TSL:1	c.252T>C	p.Gly84Gly	synonymous	Exon 2 of 2	ENSP00000401178.1

Frequencies

GnomAD3 genomes AF: 0.888 AC: 135062 AN: 152042 Hom.: 60060 Cov.: 31

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.892

GnomAD2 exomes AF: 0.891 AC: 224105 AN: 251414 AF XY: 0.885

Gnomad AFR exome AF: 0.887

Gnomad AMR exome AF: 0.948

Gnomad ASJ exome AF: 0.867

Gnomad EAS exome AF: 0.977

Gnomad FIN exome AF: 0.891

Gnomad NFE exome AF: 0.883

Gnomad OTH exome AF: 0.889

GnomAD4 exome AF: 0.885 AC: 1293587 AN: 1461466 Hom.: 573099 Cov.: 49 AF XY: 0.883 AC XY: 641698 AN XY: 727084

African (AFR) AF: 0.885 AC: 29639 AN: 33474

American (AMR) AF: 0.945 AC: 42253 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 22700 AN: 26134

East Asian (EAS) AF: 0.980 AC: 38914 AN: 39700

South Asian (SAS) AF: 0.823 AC: 71013 AN: 86250

European-Finnish (FIN) AF: 0.891 AC: 47592 AN: 53416

Middle Eastern (MID) AF: 0.834 AC: 4808 AN: 5768

European-Non Finnish (NFE) AF: 0.884 AC: 983135 AN: 1111626

Other (OTH) AF: 0.887 AC: 53533 AN: 60374

GnomAD4 genome AF: 0.888 AC: 135175 AN: 152160 Hom.: 60113 Cov.: 31 AF XY: 0.887 AC XY: 65994 AN XY: 74390

African (AFR) AF: 0.887 AC: 36834 AN: 41506

American (AMR) AF: 0.917 AC: 14016 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.867 AC: 3010 AN: 3472

East Asian (EAS) AF: 0.976 AC: 5035 AN: 5160

South Asian (SAS) AF: 0.818 AC: 3943 AN: 4818

European-Finnish (FIN) AF: 0.891 AC: 9437 AN: 10596

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.884 AC: 60085 AN: 67998

Other (OTH) AF: 0.894 AC: 1890 AN: 2114

Alfa AF: 0.885 Hom.: 48025

Bravo AF: 0.892

Asia WGS AF: 0.913 AC: 3172 AN: 3478

EpiCase AF: 0.878

EpiControl AF: 0.879

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.3
DANN	Benign	0.66
PhyloP100		4.7
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1608890; hg19: chr7-112724525; COSMIC: COSV108122460; COSMIC: COSV108122460;