Genetic Variant NM_001565.4:c.*140G>C (chr4-76021790-C-G) – 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.*140G>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 0.575 in 808,708 control chromosomes in the GnomAD database, including 139,825 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 ( 29621 hom., cov: 31)

Exomes 𝑓: 0.57 ( 110204 hom. )

Consequence

CXCL10
NM_001565.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.562

Publications

65 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=-0.9).

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 rank	MANE	Protein	UniProt
CXCL10	NM_001565.4 link	c.*140G>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000306602.3	NP_001556.2	P02778

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL10	ENST00000306602.3 link	c.*140G>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_001565.4	ENSP00000305651.1		P02778

Frequencies

GnomAD3 genomes

AF:

0.612

AC:

92983

AN:

151854

Hom.:

29564

Cov.:

show subpopulations

Gnomad AFR

AF:

0.708

Gnomad AMI

AF:

0.671

Gnomad AMR

AF:

0.717

Gnomad ASJ

AF:

0.607

Gnomad EAS

AF:

0.939

Gnomad SAS

AF:

0.550

Gnomad FIN

AF:

0.471

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.531

Gnomad OTH

AF:

0.623

GnomAD4 exome

AF:

0.566

AC:

371661

AN:

656736

Hom.:

110204

Cov.:

AF XY:

0.562

AC XY:

195616

AN XY:

347974

show subpopulations

African (AFR)

AF:

0.710

AC:

12462

AN:

17540

American (AMR)

AF:

0.806

AC:

29719

AN:

36856

Ashkenazi Jewish (ASJ)

AF:

0.616

AC:

10908

AN:

17696

East Asian (EAS)

AF:

0.935

AC:

33446

AN:

35772

South Asian (SAS)

AF:

0.527

AC:

31847

AN:

60460

European-Finnish (FIN)

AF:

0.478

AC:

24290

AN:

50794

Middle Eastern (MID)

AF:

0.581

AC:

2329

AN:

4008

European-Non Finnish (NFE)

AF:

0.518

AC:

207453

AN:

400238

Other (OTH)

AF:

0.576

AC:

19207

AN:

33372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

7273

14546

21820

29093

36366

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2702

5404

8106

10808

13510

<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:

0.613

AC:

93108

AN:

151972

Hom.:

29621

Cov.:

AF XY:

0.612

AC XY:

45490

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.708

AC:

29353

AN:

41446

American (AMR)

AF:

0.718

AC:

10963

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.607

AC:

2103

AN:

3464

East Asian (EAS)

AF:

0.939

AC:

4864

AN:

5182

South Asian (SAS)

AF:

0.551

AC:

2652

AN:

4814

European-Finnish (FIN)

AF:

0.471

AC:

4968

AN:

10542

Middle Eastern (MID)

AF:

0.585

AC:

172

AN:

294

European-Non Finnish (NFE)

AF:

0.531

AC:

36109

AN:

67940

Other (OTH)

AF:

0.624

AC:

1317

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1722

3444

5167

6889

8611

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:

0.451

Hom.:

1274

Bravo

AF:

0.641

Asia WGS

AF:

0.721

AC:

2506

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.4

(source)

DANN

Benign

0.26

PhyloP100

0.56

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