rs2256044

Positions:

• chr7-113084362-A-G
• chr7-113084362-A-T

Variant summary

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

The NM_001146267.2(GPR85):​c.360T>C​(p.Tyr120Tyr) variant causes a synonymous change. The variant allele was found at a frequency of 0.887 in 1,613,618 control chromosomes in the GnomAD database, including 635,865 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 0.90 (61511 hom., cov: 31)
  • Exomes 𝑓: 0.89 (574354 hom.)
• Consequence: GPR85 NM_001146267.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.87

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=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR85	NM_001146267.2	c.360T>C	p.Tyr120Tyr	synonymous_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.360T>C	p.Tyr120Tyr	synonymous_variant	3/3	1	NM_001146267.2	ENSP00000396763.1

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136608 AN: 152004 Hom.: 61457 Cov.: 31

Gnomad AFR AF: 0.923

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.922

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.890

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.899

GnomAD3 exomes AF: 0.894 AC: 224798 AN: 251398 Hom.: 100749 AF XY: 0.887 AC XY: 120551 AN XY: 135872

Gnomad AFR exome AF: 0.926

Gnomad AMR exome AF: 0.950

Gnomad ASJ exome AF: 0.867

Gnomad EAS exome AF: 0.977

Gnomad SAS exome AF: 0.820

Gnomad FIN exome AF: 0.891

Gnomad NFE exome AF: 0.883

Gnomad OTH exome AF: 0.889

GnomAD4 exome AF: 0.886 AC: 1295011 AN: 1461496 Hom.: 574354 Cov.: 48 AF XY: 0.883 AC XY: 642254 AN XY: 727084

Gnomad4 AFR exome AF: 0.922

Gnomad4 AMR exome AF: 0.947

Gnomad4 ASJ exome AF: 0.869

Gnomad4 EAS exome AF: 0.980

Gnomad4 SAS exome AF: 0.823

Gnomad4 FIN exome AF: 0.891

Gnomad4 NFE exome AF: 0.884

Gnomad4 OTH exome AF: 0.888

GnomAD4 genome AF: 0.899 AC: 136722 AN: 152122 Hom.: 61511 Cov.: 31 AF XY: 0.898 AC XY: 66736 AN XY: 74354

Gnomad4 AFR AF: 0.923

Gnomad4 AMR AF: 0.922

Gnomad4 ASJ AF: 0.867

Gnomad4 EAS AF: 0.976

Gnomad4 SAS AF: 0.819

Gnomad4 FIN AF: 0.890

Gnomad4 NFE AF: 0.884

Gnomad4 OTH AF: 0.900

Alfa AF: 0.887 Hom.: 80106

Bravo AF: 0.905

Asia WGS AF: 0.913 AC: 3174 AN: 3478

EpiCase AF: 0.878

EpiControl AF: 0.879

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.7
DANN	Benign	0.50

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: rs2256044; hg19: chr7-112724417;