12-12917818-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.333 AC: 2 AN: 6

Other (OTH) AF: 1.00 AC: 2 AN: 2

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

African (AFR) AF: 0.546 AC: 22645 AN: 41466

American (AMR) AF: 0.626 AC: 9558 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1823 AN: 3472

East Asian (EAS) AF: 0.873 AC: 4510 AN: 5166

South Asian (SAS) AF: 0.578 AC: 2780 AN: 4812

European-Finnish (FIN) AF: 0.432 AC: 4569 AN: 10572

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28794 AN: 67944

Other (OTH) AF: 0.507 AC: 1071 AN: 2112

Alfa AF: 0.453 Hom.: 63810

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
PhyloP100		-0.50
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: rs1056927; hg19: chr12-13070752;