Genetic Variant NM_002416.3:c.64+111G>A (chr4-76007275-C-T) – 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.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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.902

Publications

32 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:

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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=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL9	NM_002416.3	MANE Select	c.64+111G>A		intron	N/A	NP_002407.1	Q07325

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL9	ENST00000264888.6	TSL:1 MANE Select	c.64+111G>A		intron	N/A	ENSP00000354901.4	Q07325

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

30577

AN:

151950

Hom.:

3854

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.0531

AC:

898

AN:

16900

American (AMR)

AF:

0.305

AC:

12000

AN:

39366

Ashkenazi Jewish (ASJ)

AF:

0.262

AC:

5062

AN:

19304

East Asian (EAS)

AF:

0.368

AC:

13157

AN:

35732

South Asian (SAS)

AF:

0.197

AC:

12696

AN:

64298

European-Finnish (FIN)

AF:

0.285

AC:

13895

AN:

48672

Middle Eastern (MID)

AF:

0.161

AC:

645

AN:

4004

European-Non Finnish (NFE)

AF:

0.244

AC:

85760

AN:

351286

Other (OTH)

AF:

0.234

AC:

7529

AN:

32218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

5670

11339

17009

22678

28348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

802

1604

2406

3208

4010

<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:

0.201

AC:

30576

AN:

152068

Hom.:

3854

Cov.:

AF XY:

0.204

AC XY:

15147

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.0546

AC:

2266

AN:

41502

American (AMR)

AF:

0.265

AC:

4043

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.259

AC:

899

AN:

3470

East Asian (EAS)

AF:

0.376

AC:

1944

AN:

5170

South Asian (SAS)

AF:

0.202

AC:

974

AN:

4818

European-Finnish (FIN)

AF:

0.279

AC:

2949

AN:

10556

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.246

AC:

16715

AN:

67968

Other (OTH)

AF:

0.217

AC:

458

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1186

2372

3559

4745

5931

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<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:

0.120

Hom.:

467

Bravo

AF:

0.198

Asia WGS

AF:

0.242

AC:

842

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.5

(source)

DANN

Benign

0.71

PhyloP100

-0.90

PromoterAI

-0.015

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over