Genetic Variant CXCR3:c.12+213G>A (chrX-71618225-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001504.2(CXCR3):c.12+213G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00997 in 141,763 control chromosomes in the GnomAD database, including 83 homozygotes. There are 263 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.014 ( 83 hom., 261 hem., cov: 19)

Exomes 𝑓: 0.00061 ( 0 hom. 2 hem. )

Consequence

CXCR3
NM_001504.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.31

Publications

4 publications found

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 was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0893 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001504.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCR3	NM_001504.2	MANE Select	c.12+213G>A		intron	N/A	NP_001495.1	P49682-1
	CXCR3	NM_001142797.2		c.-92+213G>A		intron	N/A	NP_001136269.1	P49682-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCR3	ENST00000373693.4	TSL:1 MANE Select	c.12+213G>A		intron	N/A	ENSP00000362797.3	P49682-1
	CXCR3	ENST00000373691.4	TSL:1	c.-92+213G>A		intron	N/A	ENSP00000362795.4	P49682-2

Frequencies

GnomAD3 genomes

AF:

0.0135

AC:

1389

AN:

102544

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00311

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0863

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0996

Gnomad SAS

AF:

0.0412

Gnomad FIN

AF:

0.00639

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000920

Gnomad OTH

AF:

0.0150

GnomAD4 exome

AF:

0.000613

AC:

AN:

39172

Hom.:

AF XY:

0.000422

AC XY:

AN XY:

4740

show subpopulations

African (AFR)

AF:

0.00284

AC:

AN:

703

American (AMR)

AF:

0.0227

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

275

East Asian (EAS)

AF:

0.0421

AC:

AN:

190

South Asian (SAS)

AF:

0.00997

AC:

AN:

702

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0000279

AC:

AN:

35884

Other (OTH)

AF:

0.00386

AC:

AN:

1296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0135

AC:

1390

AN:

102591

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

261

AN XY:

25753

show subpopulations

African (AFR)

AF:

0.00310

AC:

AN:

28041

American (AMR)

AF:

0.0867

AC:

807

AN:

9304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2515

East Asian (EAS)

AF:

0.0983

AC:

309

AN:

3143

South Asian (SAS)

AF:

0.0418

AC:

AN:

2081

European-Finnish (FIN)

AF:

0.00639

AC:

AN:

5322

Middle Eastern (MID)

AF:

0.00

AC:

AN:

212

European-Non Finnish (NFE)

AF:

0.000920

AC:

AN:

49999

Other (OTH)

AF:

0.0147

AC:

AN:

1356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

107

142

178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00190

Hom.:

Bravo

AF:

0.0278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.58

(source)

DANN

Benign

0.58

PhyloP100

-1.3

PromoterAI

-0.045

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over