Variant X-71616597-C-T 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_001504.2(CXCR3):c.875G>A(p.Arg292Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,210,666 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 64 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.00016 ( 0 hom. 58 hem. )

Consequence

CXCR3
NM_001504.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.11

Variant links:

Genes affected

CXCR3 (HGNC:4540): (C-X-C motif chemokine receptor 3) This gene encodes a G protein-coupled receptor with selectivity for three chemokines, termed CXCL9/Mig (monokine induced by interferon-g), CXCL10/IP10 (interferon-g-inducible 10 kDa protein) and CXCL11/I-TAC (interferon-inducible T cell a-chemoattractant). Binding of chemokines to this protein induces cellular responses that are involved in leukocyte traffic, most notably integrin activation, cytoskeletal changes and chemotactic migration. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. One of the isoforms (CXCR3-B) shows high affinity binding to chemokine, CXCL4/PF4 (PMID:12782716). [provided by RefSeq, Jun 2011]

CXCR3 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=0.004052758).

BP6

Variant X-71616597-C-T is Benign according to our data. Variant chrX-71616597-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2660889.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCR3	NM_001504.2 linkuse as main transcript	c.875G>A	p.Arg292Gln	missense_variant	2/2	ENST00000373693.4	NP_001495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCR3	ENST00000373693.4 linkuse as main transcript	c.875G>A	p.Arg292Gln	missense_variant	2/2	1	NM_001504.2	ENSP00000362797	P1	P49682-1
CXCR3	ENST00000373691.4 linkuse as main transcript	c.1016G>A	p.Arg339Gln	missense_variant	2/2	1		ENSP00000362795		P49682-2

Frequencies

GnomAD3 genomes

AF:

0.000267

AC:

AN:

112488

Hom.:

Cov.:

AF XY:

0.000173

AC XY:

AN XY:

34636

show subpopulations

Gnomad AFR

AF:

0.0000968

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000933

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00729

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000574

AC:

105

AN:

182977

Hom.:

AF XY:

0.000518

AC XY:

AN XY:

67543

show subpopulations

Gnomad AFR exome

AF:

0.0000761

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00736

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000157

AC:

172

AN:

1098123

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

AN XY:

363509

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00516

Gnomad4 SAS exome

AF:

0.0000370

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000267

AC:

AN:

112543

Hom.:

Cov.:

AF XY:

0.000173

AC XY:

AN XY:

34701

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.0000932

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00732

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000398

Hom.:

Bravo

AF:

0.000317

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000544

AC:

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

Mar 01, 2023

CXCR3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.22

DANN

Benign

0.61

DEOGEN2

Benign

0.13

.;T

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.65

T;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.13

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.89

N;N

REVEL

Benign

0.010

Sift

Benign

0.60

T;T

Sift4G

Benign

0.29

T;T

Polyphen

0.037

B;B

Vest4

0.024

MVP

0.61

MPC

0.84

ClinPred

0.0063

GERP RS

0.48

Varity_R

0.043

gMVP

0.34

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