rs2706526

Variant names:

• chr17-74447571-G-A
• rs2706526
• NM_001438839.1:c.1296+573G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001438839.1(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_001438839.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.59
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GPRC5C	NM_022036.4	c.*543G>A		downstream_gene_variant		ENST00000392627.7	NP_071319.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPRC5C	ENST00000392627.7	c.*543G>A		downstream_gene_variant		1	NM_022036.4	ENSP00000376403.2

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

African (AFR) AF: 0.755 AC: 80 AN: 106

American (AMR) AF: 0.929 AC: 26 AN: 28

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 21 AN: 26

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 0.760 AC: 79 AN: 104

European-Finnish (FIN) AF: 0.900 AC: 9 AN: 10

Middle Eastern (MID) AF: 0.875 AC: 7 AN: 8

European-Non Finnish (NFE) AF: 0.892 AC: 4184 AN: 4692

Other (OTH) AF: 0.841 AC: 111 AN: 132

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

African (AFR) AF: 0.760 AC: 31526 AN: 41508

American (AMR) AF: 0.909 AC: 13909 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.842 AC: 2925 AN: 3472

East Asian (EAS) AF: 0.843 AC: 4368 AN: 5180

South Asian (SAS) AF: 0.825 AC: 3976 AN: 4820

European-Finnish (FIN) AF: 0.933 AC: 9887 AN: 10602

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.893 AC: 60762 AN: 68008

Other (OTH) AF: 0.851 AC: 1800 AN: 2116

Alfa AF: 0.878 Hom.: 88080

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
PhyloP100		-3.6

Splicing

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

Other links and lift over

dbSNP: rs2706526; hg19: chr17-72443710;