12-12905704-T-C

Position:

• chr12-12905704-T-C

Variant summary

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

The NM_003979.4(GPRC5A):​c.-7-2539T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 152,016 control chromosomes in the GnomAD database, including 19,990 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 (19990 hom., cov: 32)
• Consequence: GPRC5A NM_003979.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPRC5A	NM_003979.4	c.-7-2539T>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.-7-2539T>C		intron_variant		1	NM_003979.4	ENSP00000014914.6
GPRC5A	ENST00000534831.1	c.-7-2539T>C		intron_variant		3		ENSP00000441627.1
GPRC5A	ENST00000537783.1	n.107-2539T>C		intron_variant		2
GPRC5A	ENST00000542056.1	n.87-6380T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75990 AN: 151898 Hom.: 19954 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.493

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.500 AC: 76065 AN: 152016 Hom.: 19990 Cov.: 32 AF XY: 0.511 AC XY: 37939 AN XY: 74306

Gnomad4 AFR AF: 0.556

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.887

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.497

Alfa AF: 0.475 Hom.: 2196

Bravo AF: 0.510

Asia WGS AF: 0.707 AC: 2452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.81

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: rs850937; hg19: chr12-13058638;