14-105051083-C-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_013345.4(GPR132):c.1054G>T(p.Ala352Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,614,160 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 13 hom., cov: 32)

Exomes 𝑓: 0.00064 ( 13 hom. )

Consequence

GPR132
NM_013345.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.30

Variant links:

Genes affected

GPR132 (HGNC:17482): (G protein-coupled receptor 132) This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor (GPCR) superfamily. The receptors are seven-pass transmembrane proteins that respond to extracellular cues and activate intracellular signal transduction pathways. This protein was reported to be a receptor for lysophosphatidylcholine action, but PubMedID: 15653487 retracts this finding and instead suggests this protein to be an effector of lysophosphatidylcholine action. This protein may have proton-sensing activity and may be a receptor for oxidized free fatty acids. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

GPR132 links:

LOC124903398 (HGNC:):

LOC124903398 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033251941).

BP6

Variant 14-105051083-C-A is Benign according to our data. Variant chr14-105051083-C-A is described in ClinVar as [Benign]. Clinvar id is 768680.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 = 0.00687 (1046/152304) while in subpopulation AFR AF= 0.0241 (1002/41556). AF 95% confidence interval is 0.0229. There are 13 homozygotes in gnomad4. There are 479 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR132	NM_013345.4 link	c.1054G>T	p.Ala352Ser	missense_variant	Exon 4 of 4	ENST00000329797.8	NP_037477.1	Q9UNW8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR132	ENST00000329797.8 link	c.1054G>T	p.Ala352Ser	missense_variant	Exon 4 of 4	1	NM_013345.4	ENSP00000328818.3		Q9UNW8-1

Frequencies

GnomAD3 genomes

AF:

0.00688

AC:

1047

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00187

AC:

469

AN:

251366

Hom.:

AF XY:

0.00142

AC XY:

193

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.0257

Gnomad AMR exome

AF:

0.00127

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000643

AC:

940

AN:

1461856

Hom.:

Cov.:

AF XY:

0.000521

AC XY:

379

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0237

Gnomad4 AMR exome

AF:

0.00134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00124

GnomAD4 genome

AF:

0.00687

AC:

1046

AN:

152304

Hom.:

Cov.:

AF XY:

0.00643

AC XY:

479

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0241

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.00765

ESP6500AA

AF:

0.0229

AC:

101

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00236

AC:

286

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 27, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.039

DANN

Benign

0.74

DEOGEN2

Benign

0.15

T;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.36

.;T;T

MetaRNN

Benign

0.0033

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

N;.;N

PrimateAI

Benign

0.22

PROVEAN

Benign

0.19

N;N;N

REVEL

Benign

0.089

Sift

Benign

0.45

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.010

B;.;B

Vest4

0.038

MVP

0.30

MPC

0.40

ClinPred

0.0043

GERP RS

-2.4

Varity_R

0.038

gMVP

0.21

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over