chrX-71618204-C-T

Position:

• chrX-71618204-C-T

Variant summary

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

The ENST00000373693.4(CXCR3):​c.12+234G>A 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 0.24 (2485 hom., 5949 hem., cov: 19)
  • Exomes 𝑓: 0.21 (248 hom. 497 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.240 AC: 24835 AN: 103290 Hom.: 2489 Cov.: 19 AF XY: 0.224 AC XY: 5949 AN XY: 26576

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.0569

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.214

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.209 AC: 1144 AN: 5472 Hom.: 248 AF XY: 0.496 AC XY: 497 AN XY: 1002

Gnomad4 AFR exome AF: 0.280

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.286

Gnomad4 EAS exome AF: 0.400

Gnomad4 SAS exome AF: 0.524

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.197

Gnomad4 OTH exome AF: 0.253

GnomAD4 genome AF: 0.240 AC: 24829 AN: 103341 Hom.: 2485 Cov.: 19 AF XY: 0.223 AC XY: 5949 AN XY: 26637

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.211

Alfa AF: 0.222 Hom.: 11363

Bravo AF: 0.235

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.50

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

Other links and lift over

dbSNP: rs2280964; hg19: chrX-70838054;