Genetic Variant GPRC5A:c.*747T>C (chr12-12913286-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003979.4(GPRC5A):c.*747T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,716 control chromosomes in the GnomAD database, including 5,519 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 0.25 ( 5506 hom., cov: 31)

Exomes 𝑓: 0.20 ( 13 hom. )

Consequence

GPRC5A
NM_003979.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.143

Publications

16 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPRC5A	NM_003979.4 link	c.*747T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000014914.6	NP_003970.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
GPRC5A	ENST00000014914.6 link	c.*747T>C	3_prime_UTR_variant	Exon 4 of 4	1	NM_003979.4	ENSP00000014914.6
GPRC5A	ENST00000713574.1 link	c.*747T>C	3_prime_UTR_variant	Exon 4 of 4			ENSP00000518866.1
GPRC5A	ENST00000648791.1 link	c.*959T>C	3_prime_UTR_variant	Exon 3 of 3			ENSP00000497831.1
GPRC5A	ENST00000542056.1 link	n.*153T>C	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37745

AN:

151916

Hom.:

5486

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.291

Gnomad AMR

AF:

0.297

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.728

Gnomad SAS

AF:

0.311

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.211

Gnomad OTH

AF:

0.248

GnomAD4 exome

AF:

0.195

AC:

133

AN:

682

Hom.:

Cov.:

AF XY:

0.199

AC XY:

AN XY:

408

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.186

AC:

AN:

526

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.220

AC:

AN:

132

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.249

AC:

37797

AN:

152034

Hom.:

5506

Cov.:

AF XY:

0.250

AC XY:

18618

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.248

AC:

10267

AN:

41462

American (AMR)

AF:

0.298

AC:

4549

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

911

AN:

3464

East Asian (EAS)

AF:

0.728

AC:

3754

AN:

5154

South Asian (SAS)

AF:

0.311

AC:

1499

AN:

4820

European-Finnish (FIN)

AF:

0.153

AC:

1622

AN:

10586

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.211

AC:

14334

AN:

67970

Other (OTH)

AF:

0.254

AC:

535

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1381

2761

4142

5522

6903

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

394

788

1182

1576

1970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.227

Hom.:

13151

Bravo

AF:

0.261

Asia WGS

AF:

0.475

AC:

1646

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.9

(source)

DANN

Benign

0.65

PhyloP100

0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over