Variant chr7-1058177-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001303473.2(GPR146):c.662A>G(p.Asp221Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00485 in 740,280 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0051 ( 28 hom. )

Consequence

GPR146
NM_001303473.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.80

Variant links:

Genes affected

GPR146 (HGNC:21718): (G protein-coupled receptor 146) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

GPR146 links:

C7orf50 (HGNC:22421): (chromosome 7 open reading frame 50) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

C7orf50 links:

ENSG00000257607 (HGNC:):

ENSG00000257607 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01095292).

BP6

Variant 7-1058177-A-G is Benign according to our data. Variant chr7-1058177-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2657178.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR146	NM_001303473.2 linkuse as main transcript	c.662A>G	p.Asp221Gly	missense_variant	2/2	ENST00000444847.2	NP_001290402.1	Q96CH1A4D2Q3B4DTD6
C7orf50	NM_001318252.2 linkuse as main transcript	c.130-48034T>C		intron_variant		ENST00000397098.8	NP_001305181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR146	ENST00000444847.2 linkuse as main transcript	c.662A>G	p.Asp221Gly	missense_variant	2/2	2	NM_001303473.2	ENSP00000410743.2		Q96CH1
C7orf50	ENST00000397098.8 linkuse as main transcript	c.130-48034T>C		intron_variant		1	NM_001318252.2	ENSP00000380286.3		Q9BRJ6

Frequencies

GnomAD3 genomes

AF:

0.00375

AC:

571

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.000917

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00697

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00328

AC:

633

AN:

192828

Hom.:

AF XY:

0.00336

AC XY:

352

AN XY:

104854

show subpopulations

Gnomad AFR exome

AF:

0.000482

Gnomad AMR exome

AF:

0.000640

Gnomad ASJ exome

AF:

0.00430

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00575

Gnomad NFE exome

AF:

0.00583

Gnomad OTH exome

AF:

0.00270

GnomAD4 exome

AF:

0.00513

AC:

3017

AN:

588010

Hom.:

Cov.:

AF XY:

0.00527

AC XY:

1686

AN XY:

320146

show subpopulations

Gnomad4 AFR exome

AF:

0.000517

Gnomad4 AMR exome

AF:

0.000682

Gnomad4 ASJ exome

AF:

0.00342

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00616

Gnomad4 NFE exome

AF:

0.00764

Gnomad4 OTH exome

AF:

0.00359

GnomAD4 genome

AF:

0.00374

AC:

570

AN:

152270

Hom.:

Cov.:

AF XY:

0.00350

AC XY:

261

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00471

Gnomad4 NFE

AF:

0.00696

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00746

Hom.:

Bravo

AF:

0.00271

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000229

AC:

ESP6500EA

AF:

0.00432

AC:

ExAC

AF:

0.00290

AC:

347

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

C7orf50: BS2; GPR146: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.051

.;T

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.053

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

.;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

.;M

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.14

Sift

Benign

0.12

T;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.50

.;P

Vest4

0.20

MVP

0.59

MPC

0.14

ClinPred

0.061

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.20

gMVP

0.52

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