chr17-74447053-G-T

Variant names:

• chr17-74447053-G-T
• rs2706527
• NM_022036.4:c.*25G>T

Variant summary

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

The NM_022036.4(GPRC5C):​c.*25G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.882 in 1,596,592 control chromosomes in the GnomAD database, including 622,349 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 0.84 (54781 hom., cov: 34)
  • Exomes 𝑓: 0.89 (567568 hom.)
• Consequence: GPRC5C NM_022036.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.16
• Publications: 13 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022036.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPRC5C	NM_022036.4	MANE Select	c.*25G>T		3_prime_UTR	Exon 4 of 4	NP_071319.3
	GPRC5C	NM_001366262.2		c.*25G>T		3_prime_UTR	Exon 4 of 4	NP_001353191.1
	GPRC5C	NM_018653.5		c.*25G>T		3_prime_UTR	Exon 4 of 4	NP_061123.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPRC5C	ENST00000392627.7	TSL:1 MANE Select	c.*25G>T		3_prime_UTR	Exon 4 of 4	ENSP00000376403.2
	GPRC5C	ENST00000481232.2	TSL:1	c.*252G>T		3_prime_UTR	Exon 4 of 4	ENSP00000462147.2
	GPRC5C	ENST00000577663.1	TSL:6	n.1850G>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128525 AN: 152056 Hom.: 54773 Cov.: 34

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.853

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.764

Gnomad NFE AF: 0.894

Gnomad OTH AF: 0.850

GnomAD2 exomes AF: 0.876 AC: 215513 AN: 245950 AF XY: 0.874

Gnomad AFR exome AF: 0.715

Gnomad AMR exome AF: 0.934

Gnomad ASJ exome AF: 0.855

Gnomad EAS exome AF: 0.842

Gnomad FIN exome AF: 0.931

Gnomad NFE exome AF: 0.894

Gnomad OTH exome AF: 0.878

GnomAD4 exome AF: 0.886 AC: 1279077 AN: 1444418 Hom.: 567568 Cov.: 46 AF XY: 0.883 AC XY: 631757 AN XY: 715244

African (AFR) AF: 0.719 AC: 23790 AN: 33094

American (AMR) AF: 0.929 AC: 40916 AN: 44034

Ashkenazi Jewish (ASJ) AF: 0.850 AC: 21797 AN: 25646

East Asian (EAS) AF: 0.848 AC: 33337 AN: 39300

South Asian (SAS) AF: 0.823 AC: 70355 AN: 85470

European-Finnish (FIN) AF: 0.932 AC: 49349 AN: 52942

Middle Eastern (MID) AF: 0.770 AC: 4389 AN: 5700

European-Non Finnish (NFE) AF: 0.895 AC: 983600 AN: 1098828

Other (OTH) AF: 0.868 AC: 51544 AN: 59404

GnomAD4 genome AF: 0.845 AC: 128570 AN: 152174 Hom.: 54781 Cov.: 34 AF XY: 0.848 AC XY: 63121 AN XY: 74406

African (AFR) AF: 0.724 AC: 30065 AN: 41504

American (AMR) AF: 0.904 AC: 13832 AN: 15298

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

East Asian (EAS) AF: 0.842 AC: 4355 AN: 5174

South Asian (SAS) AF: 0.824 AC: 3969 AN: 4816

European-Finnish (FIN) AF: 0.932 AC: 9887 AN: 10604

Middle Eastern (MID) AF: 0.757 AC: 221 AN: 292

European-Non Finnish (NFE) AF: 0.894 AC: 60752 AN: 67988

Other (OTH) AF: 0.845 AC: 1786 AN: 2114

Alfa AF: 0.867 Hom.: 10438

Bravo AF: 0.836

Asia WGS AF: 0.776 AC: 2701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.53
PhyloP100		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2706527; hg19: chr17-72443192;