X-71618204-C-T

Variant names:

• chrX-71618204-C-T
• rs2280964
• NM_001504.2:c.12+234G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001504.2(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 NM_001504.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• Publications: 26 publications found

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

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCR3	NM_001504.2	MANE Select	c.12+234G>A		intron	N/A	NP_001495.1
	CXCR3	NM_001142797.2		c.-92+234G>A		intron	N/A	NP_001136269.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCR3	ENST00000373693.4	TSL:1 MANE Select	c.12+234G>A		intron	N/A	ENSP00000362797.3
	CXCR3	ENST00000373691.4	TSL:1	c.-92+234G>A		intron	N/A	ENSP00000362795.4

Frequencies

GnomAD3 genomes AF: 0.240 AC: 24835 AN: 103290 Hom.: 2489 Cov.: 19

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

African (AFR) AF: 0.280 AC: 26 AN: 93

American (AMR) AF: 0.500 AC: 2 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 14 AN: 49

East Asian (EAS) AF: 0.400 AC: 10 AN: 25

South Asian (SAS) AF: 0.524 AC: 55 AN: 105

European-Finnish (FIN) AF: 0.333 AC: 1 AN: 3

Middle Eastern (MID) AF: 0.200 AC: 1 AN: 5

European-Non Finnish (NFE) AF: 0.197 AC: 987 AN: 4998

Other (OTH) AF: 0.253 AC: 48 AN: 190

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

African (AFR) AF: 0.278 AC: 7791 AN: 27981

American (AMR) AF: 0.140 AC: 1367 AN: 9757

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 811 AN: 2488

East Asian (EAS) AF: 0.343 AC: 1085 AN: 3161

South Asian (SAS) AF: 0.381 AC: 790 AN: 2072

European-Finnish (FIN) AF: 0.205 AC: 1094 AN: 5330

Middle Eastern (MID) AF: 0.229 AC: 49 AN: 214

European-Non Finnish (NFE) AF: 0.229 AC: 11514 AN: 50323

Other (OTH) AF: 0.211 AC: 292 AN: 1382

Alfa AF: 0.224 Hom.: 15915

Bravo AF: 0.235

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.50
PhyloP100		-0.18
PromoterAI		-0.0020	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2280964; hg19: chrX-70838054;