rs56039557

Positions:

• chr7-113085578-C-G
• chr7-113085578-C-T

Variant summary

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

The NM_001146267.2(GPR85):​c.-171+414G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 152,266 control chromosomes in the GnomAD database, including 510 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 0.075 (510 hom., cov: 32)
• Consequence: GPR85 NM_001146267.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750

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=-0.45).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR85	NM_001146267.2	c.-171+414G>C		intron_variant		ENST00000424100.2	NP_001139739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR85	ENST00000424100.2	c.-171+414G>C		intron_variant		1	NM_001146267.2	ENSP00000396763	P1

Frequencies

GnomAD3 genomes AF: 0.0746 AC: 11357 AN: 152148 Hom.: 509 Cov.: 32

Gnomad AFR AF: 0.0423

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0530

Gnomad ASJ AF: 0.0911

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0808

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0986

Gnomad OTH AF: 0.0690

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0747 AC: 11368 AN: 152266 Hom.: 510 Cov.: 32 AF XY: 0.0746 AC XY: 5555 AN XY: 74430

Gnomad4 AFR AF: 0.0423

Gnomad4 AMR AF: 0.0529

Gnomad4 ASJ AF: 0.0911

Gnomad4 EAS AF: 0.0108

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.0808

Gnomad4 NFE AF: 0.0986

Gnomad4 OTH AF: 0.0678

Alfa AF: 0.0290 Hom.: 23

Bravo AF: 0.0684

Asia WGS AF: 0.0650 AC: 225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	11
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: rs56039557; hg19: chr7-112725633;