chr7-113083466-A-T

Position:

• chr7-113083466-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.*143T>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.06 in 744,784 control chromosomes in the GnomAD database, including 1,529 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 0.058 (308 hom., cov: 32)
  • Exomes 𝑓: 0.060 (1221 hom.)
• Consequence: GPR85 NM_001146267.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96

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=-0.49).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR85	NM_001146267.2	c.*143T>A		3_prime_UTR_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.*143T>A		3_prime_UTR_variant	3/3	1	NM_001146267.2	ENSP00000396763	P1
GPR85	ENST00000297146.7	c.*143T>A		3_prime_UTR_variant	3/3	1		ENSP00000297146	P1
GPR85	ENST00000449591.2	c.*143T>A		3_prime_UTR_variant	2/2	1		ENSP00000401178	P1
GPR85	ENST00000610164.1	c.*143T>A		3_prime_UTR_variant, NMD_transcript_variant	2/3	5		ENSP00000476863

Frequencies

GnomAD3 genomes AF: 0.0583 AC: 8864 AN: 152128 Hom.: 309 Cov.: 32

Gnomad AFR AF: 0.0599

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0687

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0707

Gnomad FIN AF: 0.0469

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0595

Gnomad OTH AF: 0.0727

GnomAD4 exome AF: 0.0605 AC: 35842 AN: 592538 Hom.: 1221 Cov.: 8 AF XY: 0.0611 AC XY: 19076 AN XY: 312298

Gnomad4 AFR exome AF: 0.0650

Gnomad4 AMR exome AF: 0.0798

Gnomad4 ASJ exome AF: 0.0535

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.0783

Gnomad4 FIN exome AF: 0.0485

Gnomad4 NFE exome AF: 0.0635

Gnomad4 OTH exome AF: 0.0641

GnomAD4 genome AF: 0.0582 AC: 8866 AN: 152246 Hom.: 308 Cov.: 32 AF XY: 0.0583 AC XY: 4338 AN XY: 74440

Gnomad4 AFR AF: 0.0598

Gnomad4 AMR AF: 0.0686

Gnomad4 ASJ AF: 0.0490

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0711

Gnomad4 FIN AF: 0.0469

Gnomad4 NFE AF: 0.0594

Gnomad4 OTH AF: 0.0714

Alfa AF: 0.0555 Hom.: 32

Bravo AF: 0.0604

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.71

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: rs870266; hg19: chr7-112723521;