rs10336

Positions:

• chr4-76001835-A-G
• chr4-76001835-A-T

Variant summary

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

The NM_002416.3(CXCL9):​c.*1763T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 161,956 control chromosomes in the GnomAD database, including 32,246 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 0.62 (30669 hom., cov: 31)
  • Exomes 𝑓: 0.55 (1577 hom.)
• Consequence: CXCL9 NM_002416.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481

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:41106): (SDAD1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCL9	NM_002416.3	c.*1763T>C		3_prime_UTR_variant	4/4	ENST00000264888.6
SDAD1-AS1	NR_125906.1	n.816-3238A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCL9	ENST00000264888.6	c.*1763T>C		3_prime_UTR_variant	4/4	1	NM_002416.3	P1
SDAD1-AS1	ENST00000501239.2	n.816-3238A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94591 AN: 151866 Hom.: 30609 Cov.: 31

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.630

GnomAD4 exome AF: 0.549 AC: 5476 AN: 9972 Hom.: 1577 Cov.: 0 AF XY: 0.552 AC XY: 2875 AN XY: 5210

Gnomad4 AFR exome AF: 0.729

Gnomad4 AMR exome AF: 0.752

Gnomad4 ASJ exome AF: 0.605

Gnomad4 EAS exome AF: 0.904

Gnomad4 SAS exome AF: 0.472

Gnomad4 FIN exome AF: 0.459

Gnomad4 NFE exome AF: 0.497

Gnomad4 OTH exome AF: 0.578

GnomAD4 genome AF: 0.623 AC: 94719 AN: 151984 Hom.: 30669 Cov.: 31 AF XY: 0.622 AC XY: 46225 AN XY: 74284

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.725

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.939

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.630

Alfa AF: 0.570 Hom.: 24209

Bravo AF: 0.652

Asia WGS AF: 0.725 AC: 2517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.67
DANN	Benign	0.31

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: rs10336; hg19: chr4-76922988;