rs3733236

Positions:

• chr4-76002845-G-A

Variant summary

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

The NM_002416.3(CXCL9):​c.*753C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 153,670 control chromosomes in the GnomAD database, including 2,046 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 0.14 (2038 hom., cov: 32)
  • Exomes 𝑓: 0.083 (8 hom.)
• Consequence: CXCL9 NM_002416.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106

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]

SDAD1-AS1 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCL9	NM_002416.3	c.*753C>T		3_prime_UTR_variant	4/4	ENST00000264888.6	NP_002407.1
SDAD1-AS1	NR_125906.1	n.816-2228G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCL9	ENST00000264888.6	c.*753C>T		3_prime_UTR_variant	4/4	1	NM_002416.3	ENSP00000354901.4
SDAD1-AS1	ENST00000501239.2	n.816-2228G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20676 AN: 152098 Hom.: 2034 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.0375

Gnomad EAS AF: 0.0577

Gnomad SAS AF: 0.0707

Gnomad FIN AF: 0.0249

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0769

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.0832 AC: 121 AN: 1454 Hom.: 8 Cov.: 0 AF XY: 0.0789 AC XY: 59 AN XY: 748

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.0116

Gnomad4 EAS exome AF: 0.0238

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0119

Gnomad4 NFE exome AF: 0.0806

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.136 AC: 20708 AN: 152216 Hom.: 2038 Cov.: 32 AF XY: 0.133 AC XY: 9872 AN XY: 74438

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.0375

Gnomad4 EAS AF: 0.0581

Gnomad4 SAS AF: 0.0706

Gnomad4 FIN AF: 0.0249

Gnomad4 NFE AF: 0.0769

Gnomad4 OTH AF: 0.126

Alfa AF: 0.0912 Hom.: 1017

Bravo AF: 0.155

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.33

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: rs3733236; hg19: chr4-76923998;