Genetic Variant CXCL10:c.*783T>C (chr4-76021147-A-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.*783T>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 0.612 in 152,160 control chromosomes in the GnomAD database, including 29,545 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: 32)

Exomes 𝑓: 0.38 ( 3 hom. )

Consequence

CXCL10
NM_001565.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.190

Publications

44 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:

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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=-0.9).

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_001565.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CXCL10	NM_001565.4	MANE Select	c.*783T>C	3_prime_UTR	Exon 4 of 4	NP_001556.2
CXCL10	NR_168520.1		n.1019T>C	non_coding_transcript_exon	Exon 3 of 3
ART3	NM_001130017.3		c.-10+9827A>G	intron	N/A	NP_001123489.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CXCL10	ENST00000306602.3	TSL:1 MANE Select	c.*783T>C	3_prime_UTR	Exon 4 of 4	ENSP00000305651.1
ART3	ENST00000341029.9	TSL:1	c.-10+9827A>G	intron	N/A	ENSP00000343843.5
ART3	ENST00000513122.5	TSL:1	c.-125+9827A>G	intron	N/A	ENSP00000422287.1

Frequencies

GnomAD3 genomes

AF:

0.611

AC:

92926

AN:

151974

Hom.:

29490

Cov.:

show subpopulations

Gnomad AFR

AF:

0.705

Gnomad AMI

AF:

0.670

Gnomad AMR

AF:

0.717

Gnomad ASJ

AF:

0.607

Gnomad EAS

AF:

0.939

Gnomad SAS

AF:

0.551

Gnomad FIN

AF:

0.472

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.531

Gnomad OTH

AF:

0.620

GnomAD4 exome

AF:

0.382

AC:

AN:

Hom.:

Cov.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.382

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.612

AC:

93042

AN:

152092

Hom.:

29542

Cov.:

AF XY:

0.612

AC XY:

45481

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.705

AC:

29257

AN:

41504

American (AMR)

AF:

0.717

AC:

10955

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.607

AC:

2108

AN:

3470

East Asian (EAS)

AF:

0.939

AC:

4868

AN:

5184

South Asian (SAS)

AF:

0.551

AC:

2655

AN:

4818

European-Finnish (FIN)

AF:

0.472

AC:

4975

AN:

10548

Middle Eastern (MID)

AF:

0.585

AC:

172

AN:

294

European-Non Finnish (NFE)

AF:

0.532

AC:

36128

AN:

67972

Other (OTH)

AF:

0.621

AC:

1313

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1798

3596

5393

7191

8989

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:

0.572

Hom.:

59732

Bravo

AF:

0.640

Asia WGS

AF:

0.720

AC:

2500

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.3

(source)

DANN

Benign

0.77

PhyloP100

-0.19

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over