rs11548618

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001565.4(CXCL10):c.85C>T(p.Arg29Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00658 in 1,611,508 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R29H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0055 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0067 ( 59 hom. )

Consequence

CXCL10
NM_001565.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.79

Publications

30 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024300724).

BP6

Variant 4-76022794-G-A is Benign according to our data. Variant chr4-76022794-G-A is described in ClinVar as Benign. ClinVar VariationId is 773454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 841 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL10	NM_001565.4 link	c.85C>T	p.Arg29Cys	missense_variant	Exon 2 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.85C>T	p.Arg29Cys	missense_variant	Exon 2 of 4	1	NM_001565.4	ENSP00000305651.1		P02778

Frequencies

GnomAD3 genomes

AF:

0.00551

AC:

839

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.0106

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00861

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00582

AC:

1438

AN:

247090

AF XY:

0.00594

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00342

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.0000557

Gnomad FIN exome

AF:

0.0115

Gnomad NFE exome

AF:

0.00871

Gnomad OTH exome

AF:

0.00563

GnomAD4 exome

AF:

0.00669

AC:

9762

AN:

1459212

Hom.:

Cov.:

AF XY:

0.00656

AC XY:

4763

AN XY:

726070

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

33470

American (AMR)

AF:

0.00344

AC:

154

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00191

AC:

AN:

26128

East Asian (EAS)

AF:

0.000101

AC:

AN:

39668

South Asian (SAS)

AF:

0.00145

AC:

125

AN:

86234

European-Finnish (FIN)

AF:

0.0113

AC:

577

AN:

51170

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00761

AC:

8456

AN:

1111688

Other (OTH)

AF:

0.00578

AC:

349

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

459

918

1378

1837

2296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

282

564

846

1128

1410

<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:

0.00552

AC:

841

AN:

152296

Hom.:

Cov.:

AF XY:

0.00572

AC XY:

426

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.00125

AC:

AN:

41568

American (AMR)

AF:

0.00412

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00166

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0106

AC:

112

AN:

10600

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00860

AC:

585

AN:

68026

Other (OTH)

AF:

0.00425

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

122

163

204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<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:

0.00741

Hom.:

Bravo

AF:

0.00445

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.00129

AC:

ESP6500EA

AF:

0.00736

AC:

ExAC

AF:

0.00611

AC:

739

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.00829

EpiControl

AF:

0.00682

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 07, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.89

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.74

PhyloP100

4.8

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-7.3

REVEL

Uncertain

0.42

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.82

MVP

0.63

MPC

0.56

ClinPred

0.057

GERP RS

4.9

Varity_R

0.79

gMVP

0.88

Mutation Taster

=78/22

polymorphism

(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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over