Genetic Variant GPRC5C:c.1296+573G>A (chr17-74447571-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001438839.1(GPRC5C):c.1296+573G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 157,310 control chromosomes in the GnomAD database, including 57,960 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 0.86 ( 55946 hom., cov: 32)

Exomes 𝑓: 0.88 ( 2014 hom. )

Consequence

GPRC5C
NM_001438839.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.59

Publications

19 publications found

Variant links:

Genes affected

GPRC5C (HGNC:13309): (G protein-coupled receptor class C group 5 member C) The protein encoded by this gene is a member of the type 3 G protein-coupled receptor family. Members of this superfamily are characterized by a signature 7-transmembrane domain motif. The specific function of this protein is unknown; however, this protein may mediate the cellular effects of retinoic acid on the G protein signal transduction cascade. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GPRC5C 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=-0.94).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001438839.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GPRC5C	NM_001438839.1		c.1296+573G>A	intron	N/A	NP_001425768.1
GPRC5C	NM_001366261.2		c.1296+573G>A	intron	N/A	NP_001353190.1
GPRC5C	NM_022036.4	MANE Select	c.*543G>A	downstream_gene	N/A	NP_071319.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GPRC5C	ENST00000392628.7	TSL:5	c.1296+573G>A	intron	N/A	ENSP00000376404.3
GPRC5C	ENST00000581590.1	TSL:5	c.787-3316G>A	intron	N/A	ENSP00000463090.1
GPRC5C	ENST00000482723.1	TSL:2	n.978+573G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.855

AC:

130084

AN:

152084

Hom.:

55923

Cov.:

show subpopulations

Gnomad AFR

AF:

0.760

Gnomad AMI

AF:

0.852

Gnomad AMR

AF:

0.909

Gnomad ASJ

AF:

0.842

Gnomad EAS

AF:

0.844

Gnomad SAS

AF:

0.825

Gnomad FIN

AF:

0.933

Gnomad MID

AF:

0.772

Gnomad NFE

AF:

0.893

Gnomad OTH

AF:

0.856

GnomAD4 exome

AF:

0.885

AC:

4519

AN:

5108

Hom.:

2014

AF XY:

0.885

AC XY:

2275

AN XY:

2572

show subpopulations

African (AFR)

AF:

0.755

AC:

AN:

106

American (AMR)

AF:

0.929

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.808

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.760

AC:

AN:

104

European-Finnish (FIN)

AF:

0.900

AC:

AN:

Middle Eastern (MID)

AF:

0.875

AC:

AN:

European-Non Finnish (NFE)

AF:

0.892

AC:

4184

AN:

4692

Other (OTH)

AF:

0.841

AC:

111

AN:

132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

110

137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

118

236

354

472

590

<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:

0.855

AC:

130152

AN:

152202

Hom.:

55946

Cov.:

AF XY:

0.859

AC XY:

63873

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.760

AC:

31526

AN:

41508

American (AMR)

AF:

0.909

AC:

13909

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.842

AC:

2925

AN:

3472

East Asian (EAS)

AF:

0.843

AC:

4368

AN:

5180

South Asian (SAS)

AF:

0.825

AC:

3976

AN:

4820

European-Finnish (FIN)

AF:

0.933

AC:

9887

AN:

10602

Middle Eastern (MID)

AF:

0.765

AC:

225

AN:

294

European-Non Finnish (NFE)

AF:

0.893

AC:

60762

AN:

68008

Other (OTH)

AF:

0.851

AC:

1800

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

953

1907

2860

3814

4767

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<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:

0.878

Hom.:

88080

Bravo

AF:

0.848

Asia WGS

AF:

0.780

AC:

2716

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.010

(source)

DANN

Benign

0.27

PhyloP100

-3.6

Splicing

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