12-12908320-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003979.4(GPRC5A):c.71C>G(p.Ala24Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,613,482 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0086 ( 22 hom., cov: 32)

Exomes 𝑓: 0.00083 ( 17 hom. )

Consequence

GPRC5A
NM_003979.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0810

Publications

4 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031090975).

BP6

Variant 12-12908320-C-G is Benign according to our data. Variant chr12-12908320-C-G is described in ClinVar as [Benign]. Clinvar id is 781065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00863 (1315/152288) while in subpopulation AFR AF = 0.0302 (1257/41566). AF 95% confidence interval is 0.0289. There are 22 homozygotes in GnomAd4. There are 629 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPRC5A	NM_003979.4 link	c.71C>G	p.Ala24Gly	missense_variant	Exon 2 of 4	ENST00000014914.6	NP_003970.1	Q8NFJ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPRC5A	ENST00000014914.6 link	c.71C>G	p.Ala24Gly	missense_variant	Exon 2 of 4	1	NM_003979.4	ENSP00000014914.6		Q8NFJ5

Frequencies

GnomAD3 genomes

AF:

0.00859

AC:

1307

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0301

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00718

GnomAD2 exomes

AF:

0.00219

AC:

550

AN:

250754

AF XY:

0.00164

show subpopulations

Gnomad AFR exome

AF:

0.0306

Gnomad AMR exome

AF:

0.00122

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.000817

GnomAD4 exome

AF:

0.000827

AC:

1209

AN:

1461194

Hom.:

Cov.:

AF XY:

0.000691

AC XY:

502

AN XY:

726844

show subpopulations

African (AFR)

AF:

0.0306

AC:

1023

AN:

33478

American (AMR)

AF:

0.00130

AC:

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86110

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000288

AC:

AN:

1111622

Other (OTH)

AF:

0.00142

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

133

199

266

332

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00863

AC:

1315

AN:

152288

Hom.:

Cov.:

AF XY:

0.00845

AC XY:

629

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0302

AC:

1257

AN:

41566

American (AMR)

AF:

0.00229

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000415

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68024

Other (OTH)

AF:

0.00711

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

118

177

236

295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00139

Hom.:

Bravo

AF:

0.00928

ESP6500AA

AF:

0.0252

AC:

111

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00287

AC:

348

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 25, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.56

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.095

T;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.16

T;T;T

MetaRNN

Benign

0.0031

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.;.

PhyloP100

-0.081

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.64

N;N;.

REVEL

Benign

0.071

Sift

Benign

0.20

T;T;.

Sift4G

Benign

0.31

T;T;.

Polyphen

0.0030

B;.;.

Vest4

0.12

MVP

0.055

MPC

0.037

ClinPred

0.0068

GERP RS

-5.8

PromoterAI

-0.019

Neutral

(source)

Varity_R

0.025

gMVP

0.38

Mutation Taster

=100/0

polymorphism

(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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12-12908320-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over