chr7-113084362-A-G

Variant names:

• chr7-113084362-A-G
• rs2256044
• NM_001146267.2:c.360T>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.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
• Publications: 15 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=-0.61).
• 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 rank	MANE	Protein	UniProt
GPR85	NM_001146267.2	c.360T>C	p.Tyr120Tyr	synonymous_variant	Exon 3 of 3	ENST00000424100.2	NP_001139739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR85	ENST00000424100.2	c.360T>C	p.Tyr120Tyr	synonymous_variant	Exon 3 of 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

GnomAD2 exomes AF: 0.894 AC: 224798 AN: 251398 AF XY: 0.887

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 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

African (AFR) AF: 0.922 AC: 30866 AN: 33474

American (AMR) AF: 0.947 AC: 42334 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 22700 AN: 26136

East Asian (EAS) AF: 0.980 AC: 38916 AN: 39700

South Asian (SAS) AF: 0.823 AC: 71016 AN: 86252

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

Middle Eastern (MID) AF: 0.834 AC: 4812 AN: 5768

European-Non Finnish (NFE) AF: 0.884 AC: 983129 AN: 1111638

Other (OTH) AF: 0.888 AC: 53646 AN: 60388

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

African (AFR) AF: 0.923 AC: 38303 AN: 41484

American (AMR) AF: 0.922 AC: 14099 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.867 AC: 3006 AN: 3468

East Asian (EAS) AF: 0.976 AC: 5025 AN: 5150

South Asian (SAS) AF: 0.819 AC: 3936 AN: 4808

European-Finnish (FIN) AF: 0.890 AC: 9436 AN: 10600

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

European-Non Finnish (NFE) AF: 0.884 AC: 60094 AN: 68006

Other (OTH) AF: 0.900 AC: 1898 AN: 2108

Alfa AF: 0.892 Hom.: 189358

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
PhyloP100		6.9
Mutation Taster		=99/1	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: rs2256044; hg19: chr7-112724417; COSMIC: COSV108122459; COSMIC: COSV108122459;