7-113083393-C-T

Variant names:

• chr7-113083393-C-T
• rs56320353
• NM_001146267.2:c.*216G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001146267.2(GPR85):​c.*216G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 539,658 control chromosomes in the GnomAD database, including 77 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 0.012 (21 hom., cov: 32)
  • Exomes 𝑓: 0.015 (56 hom.)
• Consequence: GPR85 NM_001146267.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.29

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=-0.57).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0123 (1880/152254) while in subpopulation NFE AF = 0.0203 (1379/68024). AF 95% confidence interval is 0.0194. There are 21 homozygotes in GnomAd4. There are 849 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 21 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR85	NM_001146267.2	c.*216G>A		3_prime_UTR_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	c.*216G>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_001146267.2	ENSP00000396763.1

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1878 AN: 152138 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.00430

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0106

Gnomad FIN AF: 0.00264

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0203

Gnomad OTH AF: 0.0167

GnomAD4 exome AF: 0.0148 AC: 5739 AN: 387404 Hom.: 56 Cov.: 4 AF XY: 0.0149 AC XY: 3013 AN XY: 201988

Gnomad4 AFR exome AF: 0.00422 AC: 47 AN: 11134

Gnomad4 AMR exome AF: 0.00973 AC: 131 AN: 13462

Gnomad4 ASJ exome AF: 0.0106 AC: 132 AN: 12416

Gnomad4 EAS exome AF: 0.0000722 AC: 2 AN: 27716

Gnomad4 SAS exome AF: 0.0102 AC: 324 AN: 31690

Gnomad4 FIN exome AF: 0.00434 AC: 116 AN: 26702

Gnomad4 NFE exome AF: 0.0194 AC: 4651 AN: 239472

Gnomad4 Remaining exome AF: 0.0140 AC: 323 AN: 23042

GnomAD4 genome AF: 0.0123 AC: 1880 AN: 152254 Hom.: 21 Cov.: 32 AF XY: 0.0114 AC XY: 849 AN XY: 74432

Gnomad4 AFR AF: 0.00428 AC: 0.00428441 AN: 0.00428441

Gnomad4 AMR AF: 0.0105 AC: 0.010527 AN: 0.010527

Gnomad4 ASJ AF: 0.00922 AC: 0.00921659 AN: 0.00921659

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.0110 AC: 0.0109867 AN: 0.0109867

Gnomad4 FIN AF: 0.00264 AC: 0.00264201 AN: 0.00264201

Gnomad4 NFE AF: 0.0203 AC: 0.0202723 AN: 0.0202723

Gnomad4 OTH AF: 0.0166 AC: 0.0165563 AN: 0.0165563

Alfa AF: 0.0162 Hom.: 9

Bravo AF: 0.0125

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	11
DANN	Benign	0.67
Mutation Taster		=100/0	polymorphism

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: rs56320353; hg19: chr7-112723448;