12-12917818-A-G

Variant names:

• chr12-12917818-A-G
• rs1056927
• NM_003979.4:c.*5279A>G

Variant summary

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

The NM_003979.4(GPRC5A):​c.*5279A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 152,032 control chromosomes in the GnomAD database, including 19,963 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 0.50 (19961 hom., cov: 32)
  • Exomes 𝑓: 0.50 (2 hom.)
• Consequence: GPRC5A NM_003979.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPRC5A	NM_003979.4	c.*5279A>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000014914.6	NP_003970.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPRC5A	ENST00000014914.6	c.*5279A>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_003979.4	ENSP00000014914.6

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76215 AN: 151902 Hom.: 19924 Cov.: 32

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.504

GnomAD4 exome AF: 0.500 AC: 6 AN: 12 Hom.: 2 Cov.: 0 AF XY: 0.500 AC XY: 5 AN XY: 10

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.502 AC: 76298 AN: 152020 Hom.: 19961 Cov.: 32 AF XY: 0.510 AC XY: 37868 AN XY: 74292

Gnomad4 AFR AF: 0.546

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.873

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.507

Alfa AF: 0.447 Hom.: 27870

Bravo AF: 0.517

Asia WGS AF: 0.702 AC: 2437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs1056927; hg19: chr12-13070752;