3-98532018-C-A

Position:

• chr3-98532018-C-A

Variant summary

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

The NM_005290.4(GPR15):​c.-16C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,582,760 control chromosomes in the GnomAD database, including 11,722 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 0.10 (934 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10788 hom.)
• Consequence: GPR15 NM_005290.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110

Genes affected

GPR15 (HGNC:4469): (G protein-coupled receptor 15) This gene encodes a G protein-coupled receptor that acts as a chemokine receptor for human immunodeficiency virus type 1 and 2. The encoded protein localizes to the cell membrane. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR15	NM_005290.4	c.-16C>A		5_prime_UTR_variant	1/1	ENST00000284311.5	NP_005281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR15	ENST00000284311.5	c.-16C>A		5_prime_UTR_variant	1/1		NM_005290.4	ENSP00000284311	P1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15760 AN: 152092 Hom.: 929 Cov.: 32

Gnomad AFR AF: 0.0594

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0684

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.104

GnomAD3 exomes AF: 0.120 AC: 27829 AN: 232824 Hom.: 1810 AF XY: 0.120 AC XY: 15122 AN XY: 125770

Gnomad AFR exome AF: 0.0610

Gnomad AMR exome AF: 0.136

Gnomad ASJ exome AF: 0.0716

Gnomad EAS exome AF: 0.119

Gnomad SAS exome AF: 0.140

Gnomad FIN exome AF: 0.120

Gnomad NFE exome AF: 0.122

Gnomad OTH exome AF: 0.121

GnomAD4 exome AF: 0.121 AC: 172985 AN: 1430550 Hom.: 10788 Cov.: 31 AF XY: 0.121 AC XY: 85316 AN XY: 707778

Gnomad4 AFR exome AF: 0.0590

Gnomad4 AMR exome AF: 0.132

Gnomad4 ASJ exome AF: 0.0688

Gnomad4 EAS exome AF: 0.152

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.123

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.118

GnomAD4 genome AF: 0.104 AC: 15793 AN: 152210 Hom.: 934 Cov.: 32 AF XY: 0.106 AC XY: 7858 AN XY: 74422

Gnomad4 AFR AF: 0.0596

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.0684

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.107

Alfa AF: 0.112 Hom.: 587

Bravo AF: 0.0993

Asia WGS AF: 0.185 AC: 642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.5
DANN	Benign	0.59

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: rs3749260; hg19: chr3-98250862;