X-71618204-C-G

Position:

• chrX-71618204-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000373693.4(CXCR3):​c.12+234G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0062 (4 hom., 163 hem., cov: 19)
  • Exomes 𝑓: 0.013 (2 hom. 29 hem.)
  • Failed GnomAD Quality Control
• Consequence: CXCR3 ENST00000373693.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS2: High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCR3	NM_001504.2	c.12+234G>C		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+234G>C		intron_variant		1	NM_001504.2	ENSP00000362797	P1
CXCR3	ENST00000373691.4	c.-92+234G>C		intron_variant		1		ENSP00000362795

Frequencies

GnomAD3 genomes AF: 0.00617 AC: 638 AN: 103358 Hom.: 4 Cov.: 19 AF XY: 0.00612 AC XY: 163 AN XY: 26620

Gnomad AFR AF: 0.00154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00287

Gnomad ASJ AF: 0.00201

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000480

Gnomad FIN AF: 0.00281

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.00514

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0132 AC: 72 AN: 5474 Hom.: 2 AF XY: 0.0289 AC XY: 29 AN XY: 1004

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0134

Gnomad4 OTH exome AF: 0.0263

GnomAD4 genome AF: 0.00617 AC: 638 AN: 103409 Hom.: 4 Cov.: 19 AF XY: 0.00611 AC XY: 163 AN XY: 26681

Gnomad4 AFR AF: 0.00154

Gnomad4 AMR AF: 0.00287

Gnomad4 ASJ AF: 0.00201

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000482

Gnomad4 FIN AF: 0.00281

Gnomad4 NFE AF: 0.0107

Gnomad4 OTH AF: 0.00507

Alfa AF: 0.000267 Hom.: 11363

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.98
DANN	Benign	0.36

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: rs2280964; hg19: chrX-70838054;