6-116826783-G-T

Variant names:

• chr6-116826783-G-T
• rs6938235
• NM_148963.4:c.194+2037C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_148963.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPRC6A	NM_148963.4	MANE Select	c.194+2037C>A		intron	N/A	NP_683766.2	Q5T6X5-1
	GPRC6A	NM_001286355.1		c.194+2037C>A		intron	N/A	NP_001273284.1	Q5T6X5-3
	GPRC6A	NM_001286354.1		c.194+2037C>A		intron	N/A	NP_001273283.1	Q5T6X5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPRC6A	ENST00000310357.8	TSL:1 MANE Select	c.194+2037C>A		intron	N/A	ENSP00000309493.4	Q5T6X5-1
	GPRC6A	ENST00000368549.7	TSL:1	c.194+2037C>A		intron	N/A	ENSP00000357537.3	Q5T6X5-3
	GPRC6A	ENST00000530250.1	TSL:1	c.194+2037C>A		intron	N/A	ENSP00000433465.1	Q5T6X5-2

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

African (AFR) AF: 0.173 AC: 7160 AN: 41456

American (AMR) AF: 0.349 AC: 5308 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1736 AN: 3458

East Asian (EAS) AF: 0.526 AC: 2720 AN: 5168

South Asian (SAS) AF: 0.269 AC: 1294 AN: 4816

European-Finnish (FIN) AF: 0.261 AC: 2753 AN: 10552

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23357 AN: 67750

Other (OTH) AF: 0.350 AC: 739 AN: 2112

Alfa AF: 0.341 Hom.: 11838

Bravo AF: 0.307

Asia WGS AF: 0.367 AC: 1274 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.52
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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