rs6901250

chr6-116792862-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_148963.4(GPRC6A):c.2061C>T(p.Ala687=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 1,613,786 control chromosomes in the GnomAD database, including 82,768 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 0.30 (7267 hom., cov: 33)
  • Exomes 𝑓: 0.32 (75501 hom.)
• Consequence: GPRC6A NM_148963.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123

Genes affected

GPRC6A (HGNC:18510): (G protein-coupled receptor class C group 6 member A) Members of family C of the G protein-coupled receptor (GPCR) superfamily, such as GPRC6A, are characterized by an evolutionarily conserved amino acid-sensing motif linked to an intramembranous 7-transmembrane loop region. Several members of GPCR family C, including GPRC6A, also have a long N-terminal domain (summary by Pi et al., 2005 [PubMed 16199532]).[supplied by OMIM, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=-0.123 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPRC6A	NM_148963.4	c.2061C>T	p.Ala687=	synonymous_variant	6/6	ENST00000310357.8
GPRC6A	NM_001286355.1	c.1848C>T	p.Ala616=	synonymous_variant	5/5
GPRC6A	NM_001286354.1	c.1536C>T	p.Ala512=	synonymous_variant	6/6
GPRC6A	XM_017010475.2	c.1920C>T	p.Ala640=	synonymous_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPRC6A	ENST00000310357.8	c.2061C>T	p.Ala687=	synonymous_variant	6/6	1	NM_148963.4	P1
GPRC6A	ENST00000368549.7	c.1848C>T	p.Ala616=	synonymous_variant	5/5	1
GPRC6A	ENST00000530250.1	c.1536C>T	p.Ala512=	synonymous_variant	6/6	1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45370 AN: 152032 Hom.: 7277 Cov.: 33

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.346

GnomAD3 exomes AF: 0.325 AC: 81611 AN: 250936 Hom.: 14188 AF XY: 0.324 AC XY: 43931 AN XY: 135606

Gnomad AFR exome AF: 0.210

Gnomad AMR exome AF: 0.327

Gnomad ASJ exome AF: 0.477

Gnomad EAS exome AF: 0.547

Gnomad SAS exome AF: 0.261

Gnomad FIN exome AF: 0.259

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.337

GnomAD4 exome AF: 0.317 AC: 463128 AN: 1461636 Hom.: 75501 Cov.: 44 AF XY: 0.316 AC XY: 230013 AN XY: 727108

Gnomad4 AFR exome AF: 0.219

Gnomad4 AMR exome AF: 0.328

Gnomad4 ASJ exome AF: 0.475

Gnomad4 EAS exome AF: 0.521

Gnomad4 SAS exome AF: 0.261

Gnomad4 FIN exome AF: 0.264

Gnomad4 NFE exome AF: 0.313

Gnomad4 OTH exome AF: 0.342

GnomAD4 genome AF: 0.298 AC: 45368 AN: 152150 Hom.: 7267 Cov.: 33 AF XY: 0.297 AC XY: 22075 AN XY: 74342

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.345

Alfa AF: 0.330 Hom.: 19438

Bravo AF: 0.305

Asia WGS AF: 0.370 AC: 1287 AN: 3478

EpiCase AF: 0.339

EpiControl AF: 0.330

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	3.8
Dann	Benign	0.68

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: rs6901250; hg19: chr6-117114025; COSMIC: COSV59951592;