Genetic Variant CXCL10:c.189-69C>T (chr4-76022524-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_001565.4(CXCL10):c.189-69C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 1,518,272 control chromosomes in the GnomAD database, including 244,530 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 0.61 ( 29542 hom., cov: 33)

Exomes 𝑓: 0.55 ( 214988 hom. )

Consequence

CXCL10
NM_001565.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.758

Publications

21 publications found

Variant links:

Genes affected

CXCL10 (HGNC:10637): (C-X-C motif chemokine ligand 10) This antimicrobial gene encodes a chemokine of the CXC subfamily and ligand for the receptor CXCR3. Binding of this protein to CXCR3 results in pleiotropic effects, including stimulation of monocytes, natural killer and T-cell migration, and modulation of adhesion molecule expression. This gene may also be a key regulator of the 'cytokine storm' immune response to SARS-CoV-2 infection. [provided by RefSeq, Sep 2020]

CXCL10 links:

ART3 (HGNC:725): (ADP-ribosyltransferase 3 (inactive)) This gene encodes an arginine-specific ADP-ribosyltransferase. The encoded protein catalyzes a reversible reaction which modifies proteins by the addition or removal of ADP-ribose to an arginine residue to regulate the function of the modified protein. An ADP-ribosyltransferase pseudogene is located on chromosome 11. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ART3 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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL10	NM_001565.4 link	c.189-69C>T		intron_variant	Intron 2 of 3	ENST00000306602.3	NP_001556.2	P02778

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL10	ENST00000306602.3 link	c.189-69C>T		intron_variant	Intron 2 of 3	1	NM_001565.4	ENSP00000305651.1		P02778

Frequencies

GnomAD3 genomes

AF:

0.612

AC:

92936

AN:

151972

Hom.:

29490

Cov.:

show subpopulations

Gnomad AFR

AF:

0.705

Gnomad AMI

AF:

0.670

Gnomad AMR

AF:

0.717

Gnomad ASJ

AF:

0.608

Gnomad EAS

AF:

0.938

Gnomad SAS

AF:

0.550

Gnomad FIN

AF:

0.471

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.532

Gnomad OTH

AF:

0.620

GnomAD4 exome

AF:

0.553

AC:

755209

AN:

1366182

Hom.:

214988

Cov.:

AF XY:

0.552

AC XY:

376759

AN XY:

682888

show subpopulations

African (AFR)

AF:

0.715

AC:

22422

AN:

31338

American (AMR)

AF:

0.805

AC:

34883

AN:

43324

Ashkenazi Jewish (ASJ)

AF:

0.619

AC:

15684

AN:

25350

East Asian (EAS)

AF:

0.936

AC:

36618

AN:

39118

South Asian (SAS)

AF:

0.529

AC:

44250

AN:

83646

European-Finnish (FIN)

AF:

0.480

AC:

22412

AN:

46740

Middle Eastern (MID)

AF:

0.593

AC:

3304

AN:

5574

European-Non Finnish (NFE)

AF:

0.525

AC:

542847

AN:

1033882

Other (OTH)

AF:

0.573

AC:

32789

AN:

57210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

16352

32704

49055

65407

81759

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15420

30840

46260

61680

77100

<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:

0.612

AC:

93052

AN:

152090

Hom.:

29542

Cov.:

AF XY:

0.612

AC XY:

45463

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.705

AC:

29258

AN:

41486

American (AMR)

AF:

0.717

AC:

10956

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.608

AC:

2109

AN:

3468

East Asian (EAS)

AF:

0.939

AC:

4869

AN:

5188

South Asian (SAS)

AF:

0.551

AC:

2655

AN:

4820

European-Finnish (FIN)

AF:

0.471

AC:

4970

AN:

10546

Middle Eastern (MID)

AF:

0.585

AC:

172

AN:

294

European-Non Finnish (NFE)

AF:

0.532

AC:

36141

AN:

67988

Other (OTH)

AF:

0.621

AC:

1311

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1773

3546

5320

7093

8866

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

752

1504

2256

3008

3760

<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:

0.604

Hom.:

5558

Bravo

AF:

0.640

Asia WGS

AF:

0.721

AC:

2505

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.46

PhyloP100

0.76

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over