Variant 2-240630178-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005301.5(GPR35):c.226G>A(p.Val76Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00369 in 1,590,726 control chromosomes in the GnomAD database, including 164 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.018 ( 79 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 85 hom. )

Consequence

GPR35
NM_005301.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.96

Variant links:

Genes affected

GPR35 (HGNC:4492): (G protein-coupled receptor 35) Enables C-X-C chemokine receptor activity. Involved in several processes, including chemokine-mediated signaling pathway; negative regulation of voltage-gated calcium channel activity; and positive regulation of cytosolic calcium ion concentration. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

GPR35 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022691786).

BP6

Variant 2-240630178-G-A is Benign according to our data. Variant chr2-240630178-G-A is described in ClinVar as [Benign]. Clinvar id is 791899.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GPR35	NM_005301.5 linkuse as main transcript	c.226G>A	p.Val76Met	missense_variant	2/2	ENST00000407714.2
GPR35	NM_001195381.3 linkuse as main transcript	c.319G>A	p.Val107Met	missense_variant	6/6
GPR35	NM_001195382.3 linkuse as main transcript	c.319G>A	p.Val107Met	missense_variant	6/6
GPR35	NM_001394730.1 linkuse as main transcript	c.319G>A	p.Val107Met	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR35	ENST00000407714.2 linkuse as main transcript	c.226G>A	p.Val76Met	missense_variant	2/2	1	NM_005301.5	P2	Q9HC97-1

Frequencies

GnomAD3 genomes

AF:

0.0176

AC:

2673

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0599

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00550

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.00564

AC:

1350

AN:

239472

Hom.:

AF XY:

0.00399

AC XY:

519

AN XY:

130158

show subpopulations

Gnomad AFR exome

AF:

0.0639

Gnomad AMR exome

AF:

0.00308

Gnomad ASJ exome

AF:

0.0172

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000243

Gnomad OTH exome

AF:

0.00283

GnomAD4 exome

AF:

0.00222

AC:

3190

AN:

1438470

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

1365

AN XY:

713444

show subpopulations

Gnomad4 AFR exome

AF:

0.0635

Gnomad4 AMR exome

AF:

0.00333

Gnomad4 ASJ exome

AF:

0.0177

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.0000244

Gnomad4 NFE exome

AF:

0.000135

Gnomad4 OTH exome

AF:

0.00512

GnomAD4 genome

AF:

0.0176

AC:

2674

AN:

152256

Hom.:

Cov.:

AF XY:

0.0165

AC XY:

1225

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0597

Gnomad4 AMR

AF:

0.00549

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00553

Hom.:

Bravo

AF:

0.0197

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0570

AC:

251

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.00629

AC:

763

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.57

Cadd

Benign

0.069

Dann

Benign

0.83

DEOGEN2

Benign

0.0084

T;T;.;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.012

MetaRNN

Benign

0.0023

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.12

N;N;.;N;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

0.32

N;N;N;N;.

REVEL

Benign

0.14

Sift

Benign

0.35

T;T;D;T;.

Sift4G

Benign

0.15

T;T;T;T;T

Polyphen

0.32

B;B;.;B;B

Vest4

0.026

MVP

0.25

MPC

0.29

ClinPred

0.013

GERP RS

-8.0

Varity_R

0.037

gMVP

0.13

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