rs17078383

Positions:

• chr6-116802798-C-T

Variant summary

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

The NM_148963.4(GPRC6A):​c.1336-2002G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,076 control chromosomes in the GnomAD database, including 2,061 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 0.14 (2061 hom., cov: 32)
• Consequence: GPRC6A NM_148963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPRC6A	NM_148963.4	c.1336-2002G>A		intron_variant		ENST00000310357.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPRC6A	ENST00000310357.8	c.1336-2002G>A		intron_variant		1	NM_148963.4	P1
GPRC6A	ENST00000368549.7	c.1335+3572G>A		intron_variant		1
GPRC6A	ENST00000530250.1	c.811-2002G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20550 AN: 151958 Hom.: 2055 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0849

Gnomad EAS AF: 0.00867

Gnomad SAS AF: 0.0626

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0646

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.135 AC: 20596 AN: 152076 Hom.: 2061 Cov.: 32 AF XY: 0.136 AC XY: 10082 AN XY: 74330

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.0849

Gnomad4 EAS AF: 0.00869

Gnomad4 SAS AF: 0.0624

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.0646

Gnomad4 OTH AF: 0.125

Alfa AF: 0.0783 Hom.: 959

Bravo AF: 0.147

Asia WGS AF: 0.0530 AC: 185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.69
DANN	Benign	0.73

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: rs17078383; hg19: chr6-117123961;