6-116826783-G-T

Position:

• chr6-116826783-G-T

Variant summary

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

The NM_148963.4(GPRC6A):​c.194+2037C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 151,732 control chromosomes in the GnomAD database, including 7,638 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 (7638 hom., cov: 32)
• Consequence: GPRC6A NM_148963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

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=-0.84).
• 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	Protein	UniProt
GPRC6A	NM_148963.4	c.194+2037C>A		intron_variant		ENST00000310357.8	NP_683766.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPRC6A	ENST00000310357.8	c.194+2037C>A		intron_variant		1	NM_148963.4	ENSP00000309493.4
GPRC6A	ENST00000368549.7	c.194+2037C>A		intron_variant		1		ENSP00000357537.3
GPRC6A	ENST00000530250.1	c.194+2037C>A		intron_variant		1		ENSP00000433465.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45643 AN: 151614 Hom.: 7648 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.301 AC: 45633 AN: 151732 Hom.: 7638 Cov.: 32 AF XY: 0.298 AC XY: 22097 AN XY: 74140

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.350

Alfa AF: 0.349 Hom.: 9573

Bravo AF: 0.307

Asia WGS AF: 0.367 AC: 1274 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.52

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: rs6938235; hg19: chr6-117147946; COSMIC: COSV59953700;