dbSNP rs3733236: CXCL9:c.*753C>T (chr4-76002845-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.106

Publications

28 publications found

Variant links:

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]

CXCL9 links:

SDAD1-AS1 (HGNC:41106): (SDAD1 antisense RNA 1)

SDAD1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CXCL9	NM_002416.3 link	c.*753C>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000264888.6	NP_002407.1	Q07325
SDAD1-AS1	NR_125906.1 link	n.816-2228G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL9	ENST00000264888.6 link	c.*753C>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_002416.3	ENSP00000354901.4		Q07325
SDAD1-AS1	ENST00000501239.2 link	n.816-2228G>A		intron_variant	Intron 2 of 2	1

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

20676

AN:

152098

Hom.:

2034

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.0789

AC XY:

AN XY:

748

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.150

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.0116

AC:

AN:

East Asian (EAS)

AF:

0.0238

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0119

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0806

AC:

AN:

1042

Other (OTH)

AF:

0.153

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.136

AC:

20708

AN:

152216

Hom.:

2038

Cov.:

AF XY:

0.133

AC XY:

9872

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.280

AC:

11629

AN:

41498

American (AMR)

AF:

0.163

AC:

2496

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0375

AC:

130

AN:

3470

East Asian (EAS)

AF:

0.0581

AC:

301

AN:

5184

South Asian (SAS)

AF:

0.0706

AC:

341

AN:

4832

European-Finnish (FIN)

AF:

0.0249

AC:

264

AN:

10616

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0769

AC:

5232

AN:

68012

Other (OTH)

AF:

0.126

AC:

266

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

861

1722

2583

3444

4305

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

216

432

648

864

1080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0985

Hom.:

1531

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

(source)

DANN

Benign

0.33

PhyloP100

-0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over