12-12901383-A-G

Variant names:

• chr12-12901383-A-G
• rs1548837
• NM_003979.4:c.-7-6860A>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.-7-6860A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,916 control chromosomes in the GnomAD database, including 8,989 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 0.30 (8989 hom., cov: 30)
• Consequence: GPRC5A NM_003979.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.75
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPRC5A	NM_003979.4	c.-7-6860A>G		intron_variant	Intron 1 of 3	ENST00000014914.6	NP_003970.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPRC5A	ENST00000014914.6	c.-7-6860A>G		intron_variant	Intron 1 of 3	1	NM_003979.4	ENSP00000014914.6

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46194 AN: 151798 Hom.: 9002 Cov.: 30

Gnomad AFR AF: 0.0847

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.304 AC: 46170 AN: 151916 Hom.: 8989 Cov.: 30 AF XY: 0.319 AC XY: 23642 AN XY: 74188

African (AFR) AF: 0.0845 AC: 3505 AN: 41494

American (AMR) AF: 0.458 AC: 6984 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1397 AN: 3468

East Asian (EAS) AF: 0.741 AC: 3807 AN: 5138

South Asian (SAS) AF: 0.442 AC: 2122 AN: 4800

European-Finnish (FIN) AF: 0.452 AC: 4748 AN: 10516

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22405 AN: 67940

Other (OTH) AF: 0.345 AC: 729 AN: 2110

Alfa AF: 0.338 Hom.: 7930

Bravo AF: 0.295

Asia WGS AF: 0.532 AC: 1848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0040
DANN	Benign	0.19
PhyloP100		-2.7
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: rs1548837; hg19: chr12-13054317;