dbSNP rs72637739: GPR157:p.Arg218Cys (chr1-9105626-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_024980.5(GPR157):c.652C>T(p.Arg218Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,612,300 control chromosomes in the GnomAD database, including 37,052 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.17 ( 2844 hom., cov: 32)

Exomes 𝑓: 0.21 ( 34208 hom. )

Consequence

GPR157
NM_024980.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.60

Publications

20 publications found

Variant links:

Genes affected

GPR157 (HGNC:23687): (G protein-coupled receptor 157) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway and radial glial cell differentiation. Predicted to be located in ciliary membrane. [provided by Alliance of Genome Resources, Apr 2022]

GPR157 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.005061507).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR157	NM_024980.5 link	c.652C>T	p.Arg218Cys	missense_variant	Exon 3 of 4	ENST00000377411.5	NP_079256.4	Q5UAW9
GPR157	XM_005263496.6 link	c.613C>T	p.Arg205Cys	missense_variant	Exon 3 of 4		XP_005263553.1
GPR157	XR_007063977.1 link	n.727C>T		non_coding_transcript_exon_variant	Exon 3 of 5
GPR157	XM_005263497.6 link	c.598-992C>T		intron_variant	Intron 2 of 2		XP_005263554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR157	ENST00000377411.5 link	c.652C>T	p.Arg218Cys	missense_variant	Exon 3 of 4	1	NM_024980.5	ENSP00000366628.4		Q5UAW9
GPR157	ENST00000465853.1 link	c.94-992C>T		intron_variant	Intron 1 of 1	5		ENSP00000468362.1		K7ERQ3

Frequencies

GnomAD3 genomes

AF:

0.172

AC:

26129

AN:

152024

Hom.:

2844

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0436

Gnomad AMI

AF:

0.327

Gnomad AMR

AF:

0.249

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.190

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.221

Gnomad OTH

AF:

0.193

GnomAD2 exomes

AF:

0.213

AC:

52536

AN:

246682

AF XY:

0.210

show subpopulations

Gnomad AFR exome

AF:

0.0400

Gnomad AMR exome

AF:

0.314

Gnomad ASJ exome

AF:

0.165

Gnomad EAS exome

AF:

0.201

Gnomad FIN exome

AF:

0.247

Gnomad NFE exome

AF:

0.217

Gnomad OTH exome

AF:

0.219

GnomAD4 exome

AF:

0.213

AC:

310626

AN:

1460158

Hom.:

34208

Cov.:

AF XY:

0.212

AC XY:

153765

AN XY:

726198

show subpopulations

African (AFR)

AF:

0.0351

AC:

1174

AN:

33478

American (AMR)

AF:

0.306

AC:

13586

AN:

44448

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

4430

AN:

26004

East Asian (EAS)

AF:

0.202

AC:

8025

AN:

39650

South Asian (SAS)

AF:

0.169

AC:

14531

AN:

85768

European-Finnish (FIN)

AF:

0.243

AC:

12974

AN:

53354

Middle Eastern (MID)

AF:

0.238

AC:

1372

AN:

5762

European-Non Finnish (NFE)

AF:

0.218

AC:

242488

AN:

1111356

Other (OTH)

AF:

0.200

AC:

12046

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

12545

25090

37636

50181

62726

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8360

16720

25080

33440

41800

<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:

0.172

AC:

26120

AN:

152142

Hom.:

2844

Cov.:

AF XY:

0.173

AC XY:

12875

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0435

AC:

1805

AN:

41538

American (AMR)

AF:

0.249

AC:

3800

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

552

AN:

3470

East Asian (EAS)

AF:

0.189

AC:

977

AN:

5160

South Asian (SAS)

AF:

0.144

AC:

695

AN:

4816

European-Finnish (FIN)

AF:

0.238

AC:

2523

AN:

10596

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.221

AC:

15015

AN:

67966

Other (OTH)

AF:

0.191

AC:

403

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1081

2162

3242

4323

5404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

282

564

846

1128

1410

<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:

0.199

Hom.:

7511

Bravo

AF:

0.168

TwinsUK

AF:

0.214

AC:

795

ALSPAC

AF:

0.210

AC:

808

ESP6500AA

AF:

0.0499

AC:

220

ESP6500EA

AF:

0.220

AC:

1889

ExAC

AF:

0.204

AC:

24776

Asia WGS

AF:

0.159

AC:

553

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.051

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0051

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

2.6

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.7

REVEL

Benign

0.050

Sift

Benign

0.037

Sift4G

Uncertain

0.021

Polyphen

0.068

Vest4

0.073

MPC

0.11

ClinPred

0.013

GERP RS

1.8

Varity_R

0.072

gMVP

0.67

Mutation Taster

=94/6

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