rs2241228

Positions:

• chr12-12892053-T-C
• chr12-12892053-T-G

Variant summary

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

The NM_003979.4(GPRC5A):​c.-8+389T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 151,168 control chromosomes in the GnomAD database, including 22,014 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 0.53 (21969 hom., cov: 29)
  • Exomes 𝑓: 0.58 (45 hom.)
• Consequence: GPRC5A NM_003979.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

Genes affected

GPRC5A (HGNC:9836): (G protein-coupled receptor class C group 5 member A) This gene encodes a member of the type 3 G protein-coupling receptor family, characterized by the signature 7-transmembrane domain motif. The encoded protein may be involved in interaction between retinoid acid and G protein signalling pathways. Retinoic acid plays a critical role in development, cellular growth, and differentiation. This gene may play a role in embryonic development and epithelial cell differentiation. [provided by RefSeq, Jul 2008]

GPRC5A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPRC5A	NM_003979.4	c.-8+389T>C		intron_variant		ENST00000014914.6	NP_003970.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPRC5A	ENST00000014914.6	c.-8+389T>C		intron_variant		1	NM_003979.4	ENSP00000014914.6
GPRC5A	ENST00000534831.1	c.-8+11T>C		intron_variant		3		ENSP00000441627.1
GPRC5A	ENST00000537783.1	n.106+389T>C		intron_variant		2
GPRC5A	ENST00000542056.1	n.86+389T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.534 AC: 80469 AN: 150792 Hom.: 21965 Cov.: 29

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.501

GnomAD4 exome AF: 0.577 AC: 150 AN: 260 Hom.: 45 Cov.: 0 AF XY: 0.572 AC XY: 79 AN XY: 138

Gnomad4 AFR exome AF: 0.667

Gnomad4 ASJ exome AF: 0.500

Gnomad4 FIN exome AF: 0.595

Gnomad4 NFE exome AF: 0.615

Gnomad4 OTH exome AF: 0.417

GnomAD4 genome AF: 0.533 AC: 80500 AN: 150908 Hom.: 21969 Cov.: 29 AF XY: 0.531 AC XY: 39131 AN XY: 73730

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.566

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.499

Alfa AF: 0.551 Hom.: 6024

Bravo AF: 0.528

Asia WGS AF: 0.381 AC: 1330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.8
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2241228; hg19: chr12-13044987;