rs2706526

Positions:

• chr17-74447571-G-A

Variant summary

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

The NM_001366261.2(GPRC5C):​c.1296+573G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 157,310 control chromosomes in the GnomAD database, including 57,960 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 0.86 (55946 hom., cov: 32)
  • Exomes 𝑓: 0.88 (2014 hom.)
• Consequence: GPRC5C NM_001366261.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.59

Genes affected

GPRC5C (HGNC:13309): (G protein-coupled receptor class C group 5 member C) The protein encoded by this gene is a member of the type 3 G protein-coupled receptor family. Members of this superfamily are characterized by a signature 7-transmembrane domain motif. The specific function of this protein is unknown; however, this protein may mediate the cellular effects of retinoic acid on the G protein signal transduction cascade. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPRC5C	NM_001366261.2	c.1296+573G>A		intron_variant			NP_001353190.1
GPRC5C	XM_047436398.1	c.1596+573G>A		intron_variant			XP_047292354.1
GPRC5C	XM_047436399.1	c.1296+573G>A		intron_variant			XP_047292355.1
GPRC5C	XM_047436400.1	c.1296+573G>A		intron_variant			XP_047292356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPRC5C	ENST00000392628.7	c.1296+573G>A		intron_variant		5		ENSP00000376404	A1
GPRC5C	ENST00000581590.1	c.788-3316G>A		intron_variant		5		ENSP00000463090
GPRC5C	ENST00000482723.1	n.978+573G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.855 AC: 130084 AN: 152084 Hom.: 55923 Cov.: 32

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.909

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.933

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.893

Gnomad OTH AF: 0.856

GnomAD4 exome AF: 0.885 AC: 4519 AN: 5108 Hom.: 2014 AF XY: 0.885 AC XY: 2275 AN XY: 2572

Gnomad4 AFR exome AF: 0.755

Gnomad4 AMR exome AF: 0.929

Gnomad4 ASJ exome AF: 0.808

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.760

Gnomad4 FIN exome AF: 0.900

Gnomad4 NFE exome AF: 0.892

Gnomad4 OTH exome AF: 0.841

GnomAD4 genome AF: 0.855 AC: 130152 AN: 152202 Hom.: 55946 Cov.: 32 AF XY: 0.859 AC XY: 63873 AN XY: 74398

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.909

Gnomad4 ASJ AF: 0.842

Gnomad4 EAS AF: 0.843

Gnomad4 SAS AF: 0.825

Gnomad4 FIN AF: 0.933

Gnomad4 NFE AF: 0.893

Gnomad4 OTH AF: 0.851

Alfa AF: 0.883 Hom.: 61230

Bravo AF: 0.848

Asia WGS AF: 0.780 AC: 2716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.010
DANN	Benign	0.27

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2706526; hg19: chr17-72443710;