chrX-71618225-C-T

Position:

• chrX-71618225-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCR3	NM_001504.2	c.12+213G>A		intron_variant		ENST00000373693.4	NP_001495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCR3	ENST00000373693.4	c.12+213G>A		intron_variant		1	NM_001504.2	ENSP00000362797	P1
CXCR3	ENST00000373691.4	c.-92+213G>A		intron_variant		1		ENSP00000362795

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 1389 AN: 102544 Hom.: 81 Cov.: 19 AF XY: 0.0101 AC XY: 259 AN XY: 25696

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: 24 AN: 39172 Hom.: 0 AF XY: 0.000422 AC XY: 2 AN XY: 4740

Gnomad4 AFR exome AF: 0.00284

Gnomad4 AMR exome AF: 0.0227

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0421

Gnomad4 SAS exome AF: 0.00997

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000279

Gnomad4 OTH exome AF: 0.00386

GnomAD4 genome AF: 0.0135 AC: 1390 AN: 102591 Hom.: 83 Cov.: 19 AF XY: 0.0101 AC XY: 261 AN XY: 25753

Gnomad4 AFR AF: 0.00310

Gnomad4 AMR AF: 0.0867

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0983

Gnomad4 SAS AF: 0.0418

Gnomad4 FIN AF: 0.00639

Gnomad4 NFE AF: 0.000920

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00190 Hom.: 16

Bravo AF: 0.0278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.58
DANN	Benign	0.58

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

LitVar

Other links and lift over

dbSNP: rs34334103; hg19: chrX-70838075;