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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003979.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPRC5A	NM_003979.4	MANE Select	c.*747T>C		3_prime_UTR	Exon 4 of 4	NP_003970.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GPRC5A	ENST00000014914.6	TSL:1 MANE Select	c.*747T>C	3_prime_UTR	Exon 4 of 4	ENSP00000014914.6
GPRC5A	ENST00000713574.1		c.*747T>C	3_prime_UTR	Exon 4 of 4	ENSP00000518866.1
GPRC5A	ENST00000648791.1		c.*959T>C	3_prime_UTR	Exon 3 of 3	ENSP00000497831.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over