4-76007275-C-T

Position:

• chr4-76007275-C-T

Variant summary

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

The NM_002416.3(CXCL9):​c.64+111G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 763,848 control chromosomes in the GnomAD database, including 23,650 homozygotes. 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 0.20 (3854 hom., cov: 32)
  • Exomes 𝑓: 0.25 (19796 hom.)
• Consequence: CXCL9 NM_002416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.902

Genes affected

CXCL9 (HGNC:7098): (C-X-C motif chemokine ligand 9) This antimicrobial gene is part of a chemokine superfamily that encodes secreted proteins involved in immunoregulatory and inflammatory processes. The protein encoded is thought to be involved in T cell trafficking. The encoded protein binds to C-X-C motif chemokine 3 and is a chemoattractant for lymphocytes but not for neutrophils. [provided by RefSeq, Aug 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCL9	NM_002416.3	c.64+111G>A		intron_variant		ENST00000264888.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCL9	ENST00000264888.6	c.64+111G>A		intron_variant		1	NM_002416.3	P1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30577 AN: 151950 Hom.: 3854 Cov.: 32

Gnomad AFR AF: 0.0547

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.217

GnomAD4 exome AF: 0.248 AC: 151642 AN: 611780 Hom.: 19796 AF XY: 0.245 AC XY: 80867 AN XY: 330548

Gnomad4 AFR exome AF: 0.0531

Gnomad4 AMR exome AF: 0.305

Gnomad4 ASJ exome AF: 0.262

Gnomad4 EAS exome AF: 0.368

Gnomad4 SAS exome AF: 0.197

Gnomad4 FIN exome AF: 0.285

Gnomad4 NFE exome AF: 0.244

Gnomad4 OTH exome AF: 0.234

GnomAD4 genome AF: 0.201 AC: 30576 AN: 152068 Hom.: 3854 Cov.: 32 AF XY: 0.204 AC XY: 15147 AN XY: 74312

Gnomad4 AFR AF: 0.0546

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.217

Alfa AF: 0.157 Hom.: 422

Bravo AF: 0.198

Asia WGS AF: 0.242 AC: 842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.5
DANN	Benign	0.71

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: rs2276886; hg19: chr4-76928428; COSMIC: COSV53578976; COSMIC: COSV53578976;