Variant X-71617566-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 ENST00000373691.4(CXCR3):c.47T>C(p.Ile16Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000325 in 1,139,556 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000034 ( 0 hom. 11 hem. )

Consequence

CXCR3
ENST00000373691.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.306

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=0.00741601).

BP6

Variant X-71617566-A-G is Benign according to our data. Variant chrX-71617566-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3270418.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCR3	NM_001504.2 linkuse as main transcript	c.13-107T>C		intron_variant		ENST00000373693.4	NP_001495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCR3	ENST00000373691.4 linkuse as main transcript	c.47T>C	p.Ile16Thr	missense_variant	2/2	1		ENSP00000362795		P49682-2
CXCR3	ENST00000373693.4 linkuse as main transcript	c.13-107T>C		intron_variant		1	NM_001504.2	ENSP00000362797	P1	P49682-1

Frequencies

GnomAD3 genomes

AF:

0.0000181

AC:

AN:

110385

Hom.:

Cov.:

AF XY:

0.0000306

AC XY:

AN XY:

32635

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000573

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:

0.000232

AC:

AN:

90508

Hom.:

AF XY:

0.000288

AC XY:

AN XY:

27794

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00251

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000310

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000340

AC:

AN:

1029118

Hom.:

Cov.:

AF XY:

0.0000333

AC XY:

AN XY:

330180

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000889

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000112

Gnomad4 OTH exome

AF:

0.0000460

GnomAD4 genome

AF:

0.0000181

AC:

AN:

110438

Hom.:

Cov.:

AF XY:

0.0000306

AC XY:

AN XY:

32698

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000575

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000132

ExAC

AF:

0.0000702

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

Jun 05, 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

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.5

DANN

Benign

0.32

FATHMM_MKL

Benign

0.0050

LIST_S2

Benign

0.23

M_CAP

Benign

0.044

MetaRNN

Benign

0.0074

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

0.040

REVEL

Benign

0.044

Sift

Benign

0.39

Polyphen

0.0

Vest4

0.015

MutPred

0.40

Gain of disorder (P = 0.0049);

MVP

0.36

MPC

0.91

ClinPred

0.023

GERP RS

-2.8

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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