Genetic Variant NM_005301.5:c.880A>C (chr2-240630832-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005301.5(GPR35):c.880A>C(p.Ser294Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 1,612,842 control chromosomes in the GnomAD database, including 265,508 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S294N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.47 ( 19054 hom., cov: 33)

Exomes 𝑓: 0.57 ( 246454 hom. )

Consequence

GPR35
NM_005301.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.16

Publications

52 publications found

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 was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=1.4194889E-6).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR35	NM_005301.5 link	c.880A>C	p.Ser294Arg	missense_variant	Exon 2 of 2	ENST00000407714.2	NP_005292.2	Q9HC97-1B2RA17A8K2J1
GPR35	NM_001195381.3 link	c.973A>C	p.Ser325Arg	missense_variant	Exon 6 of 6		NP_001182310.1	Q9HC97-2
GPR35	NM_001195382.3 link	c.973A>C	p.Ser325Arg	missense_variant	Exon 6 of 6		NP_001182311.1	Q9HC97-2A8K2J1
GPR35	NM_001394730.1 link	c.973A>C	p.Ser325Arg	missense_variant	Exon 6 of 6		NP_001381659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR35	ENST00000407714.2 link	c.880A>C	p.Ser294Arg	missense_variant	Exon 2 of 2	1	NM_005301.5	ENSP00000384263.1		Q9HC97-1

Frequencies

GnomAD3 genomes

AF:

0.475

AC:

72152

AN:

151968

Hom.:

19036

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.536

Gnomad AMR

AF:

0.395

Gnomad ASJ

AF:

0.486

Gnomad EAS

AF:

0.699

Gnomad SAS

AF:

0.783

Gnomad FIN

AF:

0.584

Gnomad MID

AF:

0.509

Gnomad NFE

AF:

0.573

Gnomad OTH

AF:

0.481

GnomAD2 exomes

AF:

0.555

AC:

139371

AN:

250952

AF XY:

0.578

show subpopulations

Gnomad AFR exome

AF:

0.241

Gnomad AMR exome

AF:

0.394

Gnomad ASJ exome

AF:

0.481

Gnomad EAS exome

AF:

0.703

Gnomad FIN exome

AF:

0.586

Gnomad NFE exome

AF:

0.567

Gnomad OTH exome

AF:

0.537

GnomAD4 exome

AF:

0.574

AC:

838815

AN:

1460756

Hom.:

246454

Cov.:

AF XY:

0.582

AC XY:

423113

AN XY:

726690

show subpopulations

African (AFR)

AF:

0.246

AC:

8226

AN:

33480

American (AMR)

AF:

0.391

AC:

17502

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.483

AC:

12633

AN:

26132

East Asian (EAS)

AF:

0.711

AC:

28235

AN:

39698

South Asian (SAS)

AF:

0.776

AC:

66944

AN:

86256

European-Finnish (FIN)

AF:

0.585

AC:

30622

AN:

52374

Middle Eastern (MID)

AF:

0.531

AC:

3061

AN:

5768

European-Non Finnish (NFE)

AF:

0.573

AC:

637629

AN:

1111948

Other (OTH)

AF:

0.563

AC:

33963

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

21282

42563

63845

85126

106408

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17622

35244

52866

70488

88110

<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:

0.475

AC:

72187

AN:

152086

Hom.:

19054

Cov.:

AF XY:

0.480

AC XY:

35678

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.248

AC:

10286

AN:

41478

American (AMR)

AF:

0.395

AC:

6037

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.486

AC:

1687

AN:

3470

East Asian (EAS)

AF:

0.700

AC:

3611

AN:

5162

South Asian (SAS)

AF:

0.782

AC:

3770

AN:

4818

European-Finnish (FIN)

AF:

0.584

AC:

6181

AN:

10586

Middle Eastern (MID)

AF:

0.514

AC:

151

AN:

294

European-Non Finnish (NFE)

AF:

0.573

AC:

38953

AN:

67980

Other (OTH)

AF:

0.486

AC:

1024

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1855

3710

5566

7421

9276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

664

1328

1992

2656

3320

<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:

0.534

Hom.:

48944

Bravo

AF:

0.445

TwinsUK

AF:

0.576

AC:

2136

ALSPAC

AF:

0.589

AC:

2269

ESP6500AA

AF:

0.247

AC:

1088

ESP6500EA

AF:

0.565

AC:

4857

ExAC

AF:

0.559

AC:

67823

Asia WGS

AF:

0.712

AC:

2474

AN:

3476

EpiCase

AF:

0.563

EpiControl

AF:

0.562

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.3

(source)

DANN

Benign

0.22

DEOGEN2

Benign

0.0055

T;T;.;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.28

.;.;T;.;T

MetaRNN

Benign

0.0000014

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.20

N;N;.;N;N

PhyloP100

-1.2

PrimateAI

Benign

0.28

PROVEAN

Benign

1.3

N;N;.;N;.

REVEL

Benign

0.060

Sift

Benign

0.66

T;T;.;T;.

Sift4G

Benign

0.55

T;T;T;T;T

Polyphen

0.0

B;B;.;B;B

Vest4

0.045

MutPred

0.11

Loss of ubiquitination at K299 (P = 0.0283);Loss of ubiquitination at K299 (P = 0.0283);.;Loss of ubiquitination at K299 (P = 0.0283);Loss of ubiquitination at K299 (P = 0.0283);

MPC

0.31

ClinPred

0.0013

GERP RS

-3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.053

gMVP

0.18

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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