chr2-240630212-C-T

Position:

chr2-240630212-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_005301.5(GPR35):c.260C>T(p.Pro87Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000483 in 1,573,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

GPR35
NM_005301.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.390

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.025577337).

BP6

Variant 2-240630212-C-T is Benign according to our data. Variant chr2-240630212-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3282381.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR35	NM_005301.5 linkuse as main transcript	c.260C>T	p.Pro87Leu	missense_variant	2/2	ENST00000407714.2	NP_005292.2	Q9HC97-1B2RA17A8K2J1
GPR35	NM_001195381.3 linkuse as main transcript	c.353C>T	p.Pro118Leu	missense_variant	6/6		NP_001182310.1	Q9HC97-2
GPR35	NM_001195382.3 linkuse as main transcript	c.353C>T	p.Pro118Leu	missense_variant	6/6		NP_001182311.1	Q9HC97-2A8K2J1
GPR35	NM_001394730.1 linkuse as main transcript	c.353C>T	p.Pro118Leu	missense_variant	6/6		NP_001381659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR35	ENST00000407714.2 linkuse as main transcript	c.260C>T	p.Pro87Leu	missense_variant	2/2	1	NM_005301.5	ENSP00000384263.1		Q9HC97-1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000354

AC:

AN:

225770

Hom.:

AF XY:

0.0000327

AC XY:

AN XY:

122170

show subpopulations

Gnomad AFR exome

AF:

0.000312

Gnomad AMR exome

AF:

0.0000298

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000190

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000373

AC:

AN:

1420888

Hom.:

Cov.:

AF XY:

0.0000427

AC XY:

AN XY:

702382

show subpopulations

Gnomad4 AFR exome

AF:

0.000605

Gnomad4 AMR exome

AF:

0.0000228

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000511

Gnomad4 SAS exome

AF:

0.0000721

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000201

Gnomad4 OTH exome

AF:

0.0000339

GnomAD4 genome

AF:

0.000151

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.000531

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000102

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.59

CADD

Benign

4.4

DANN

Benign

0.52

DEOGEN2

Benign

0.0089

T;T;.;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.69

.;.;T;.;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.026

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.085

N;N;.;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.030

N;N;.;N;.

REVEL

Benign

0.071

Sift

Benign

0.79

T;T;.;T;.

Sift4G

Benign

0.39

T;T;T;T;T

Polyphen

0.0070

B;B;.;B;B

Vest4

0.034

MutPred

0.54

Loss of disorder (P = 0.0319);Loss of disorder (P = 0.0319);.;Loss of disorder (P = 0.0319);Loss of disorder (P = 0.0319);

MVP

0.43

MPC

0.29

ClinPred

0.0058

GERP RS

-1.9

Varity_R

0.044

gMVP

0.12

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