Variant X-71617490-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000373691.4(CXCR3):c.123A>T(p.Thr41=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,205,255 control chromosomes in the GnomAD database, including 19 homozygotes. There are 433 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 8 hom., 102 hem., cov: 22)

Exomes 𝑓: 0.0011 ( 11 hom. 331 hem. )

Consequence

CXCR3
ENST00000373691.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.92

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant X-71617490-T-A is Benign according to our data. Variant chrX-71617490-T-A is described in ClinVar as [Benign]. Clinvar id is 770020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.92 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00273 (303/110890) while in subpopulation AMR AF= 0.0237 (249/10499). AF 95% confidence interval is 0.0213. There are 8 homozygotes in gnomad4. There are 102 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCR3	NM_001504.2 linkuse as main transcript	c.13-31A>T		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.123A>T	p.Thr41=	synonymous_variant	2/2	1		ENSP00000362795		P49682-2
CXCR3	ENST00000373693.4 linkuse as main transcript	c.13-31A>T		intron_variant		1	NM_001504.2	ENSP00000362797	P1	P49682-1

Frequencies

GnomAD3 genomes

AF:

0.00274

AC:

304

AN:

110836

Hom.:

Cov.:

AF XY:

0.00305

AC XY:

101

AN XY:

33076

show subpopulations

Gnomad AFR

AF:

0.000460

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0238

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00625

Gnomad SAS

AF:

0.000384

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000208

Gnomad OTH

AF:

0.00400

GnomAD3 exomes

AF:

0.00450

AC:

771

AN:

171396

Hom.:

AF XY:

0.00357

AC XY:

210

AN XY:

58780

show subpopulations

Gnomad AFR exome

AF:

0.000509

Gnomad AMR exome

AF:

0.0252

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00508

Gnomad SAS exome

AF:

0.000170

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000931

Gnomad OTH exome

AF:

0.00443

GnomAD4 exome

AF:

0.00109

AC:

1198

AN:

1094365

Hom.:

Cov.:

AF XY:

0.000919

AC XY:

331

AN XY:

360053

show subpopulations

Gnomad4 AFR exome

AF:

0.000531

Gnomad4 AMR exome

AF:

0.0272

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00335

Gnomad4 SAS exome

AF:

0.0000375

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000821

Gnomad4 OTH exome

AF:

0.00150

GnomAD4 genome

AF:

0.00273

AC:

303

AN:

110890

Hom.:

Cov.:

AF XY:

0.00308

AC XY:

102

AN XY:

33140

show subpopulations

Gnomad4 AFR

AF:

0.000459

Gnomad4 AMR

AF:

0.0237

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00627

Gnomad4 SAS

AF:

0.000385

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000208

Gnomad4 OTH

AF:

0.00395

Alfa

AF:

0.00116

Hom.:

Bravo

AF:

0.00438

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.023

DANN

Benign

0.83

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