4-76001835-A-G

Variant names:

• chr4-76001835-A-G
• rs10336
• NM_002416.3:c.*1763T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 49 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002416.3. 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
	CXCL9	NM_002416.3	MANE Select	c.*1763T>C		3_prime_UTR	Exon 4 of 4	NP_002407.1
	SDAD1-AS1	NR_125906.1		n.816-3238A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL9	ENST00000264888.6	TSL:1 MANE Select	c.*1763T>C		3_prime_UTR	Exon 4 of 4	ENSP00000354901.4
	SDAD1-AS1	ENST00000501239.2	TSL:1	n.816-3238A>G		intron	N/A

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

African (AFR) AF: 0.729 AC: 293 AN: 402

American (AMR) AF: 0.752 AC: 212 AN: 282

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 270 AN: 446

East Asian (EAS) AF: 0.904 AC: 629 AN: 696

South Asian (SAS) AF: 0.472 AC: 34 AN: 72

European-Finnish (FIN) AF: 0.459 AC: 361 AN: 786

Middle Eastern (MID) AF: 0.675 AC: 27 AN: 40

European-Non Finnish (NFE) AF: 0.497 AC: 3308 AN: 6656

Other (OTH) AF: 0.578 AC: 342 AN: 592

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

African (AFR) AF: 0.733 AC: 30360 AN: 41426

American (AMR) AF: 0.725 AC: 11079 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2063 AN: 3468

East Asian (EAS) AF: 0.939 AC: 4862 AN: 5176

South Asian (SAS) AF: 0.549 AC: 2636 AN: 4802

European-Finnish (FIN) AF: 0.481 AC: 5081 AN: 10572

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.538 AC: 36526 AN: 67950

Other (OTH) AF: 0.630 AC: 1327 AN: 2106

Alfa AF: 0.578 Hom.: 35879

Bravo AF: 0.652

Asia WGS AF: 0.725 AC: 2517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.67
DANN	Benign	0.31
PhyloP100		-0.48
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: rs10336; hg19: chr4-76922988;