Genetic Variant GPR37:p.Thr241Thr (chr7-124764254-C-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_005302.5(GPR37):c.723G>T(p.Thr241Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00808 in 1,598,330 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0062 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0083 ( 64 hom. )

Consequence

GPR37
NM_005302.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -8.33

Variant links:

Genes affected

GPR37 (HGNC:4494): (G protein-coupled receptor 37) This gene is a member of the G protein-coupled receptor family. The encoded protein contains seven transmembrane domains and is found in cell and endoplasmic reticulum membranes. G protein-coupled receptors are involved in translating outside signals into G protein mediated intracellular effects. This gene product interacts with Parkin and is involved in juvenile Parkinson disease. [provided by RefSeq, Oct 2012]

GPR37 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 7-124764254-C-A is Benign according to our data. Variant chr7-124764254-C-A is described in ClinVar as [Benign]. Clinvar id is 772891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-8.33 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR37	NM_005302.5 link	c.723G>T	p.Thr241Thr	synonymous_variant	Exon 1 of 2	ENST00000303921.3	NP_005293.1	O15354

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR37	ENST00000303921.3 link	c.723G>T	p.Thr241Thr	synonymous_variant	Exon 1 of 2	1	NM_005302.5	ENSP00000306449.2		O15354

Frequencies

GnomAD3 genomes

AF:

0.00622

AC:

946

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.00631

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0109

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00660

AC:

1565

AN:

237134

Hom.:

AF XY:

0.00653

AC XY:

833

AN XY:

127608

show subpopulations

Gnomad AFR exome

AF:

0.00130

Gnomad AMR exome

AF:

0.00140

Gnomad ASJ exome

AF:

0.00735

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00261

Gnomad FIN exome

AF:

0.00491

Gnomad NFE exome

AF:

0.0114

Gnomad OTH exome

AF:

0.00494

GnomAD4 exome

AF:

0.00828

AC:

11977

AN:

1446036

Hom.:

Cov.:

AF XY:

0.00822

AC XY:

5900

AN XY:

717778

show subpopulations

Gnomad4 AFR exome

AF:

0.00118

Gnomad4 AMR exome

AF:

0.00146

Gnomad4 ASJ exome

AF:

0.00761

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00245

Gnomad4 FIN exome

AF:

0.00602

Gnomad4 NFE exome

AF:

0.00978

Gnomad4 OTH exome

AF:

0.00594

GnomAD4 genome

AF:

0.00621

AC:

945

AN:

152294

Hom.:

Cov.:

AF XY:

0.00585

AC XY:

436

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00631

Gnomad4 NFE

AF:

0.0109

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00848

Hom.:

Bravo

AF:

0.00560

Asia WGS

AF:

0.00375

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

Jul 10, 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

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.20

DANN

Benign

0.39

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