4-76035093-T-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005409.5(CXCL11):c.215A>G(p.Gln72Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000206 in 1,601,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

CXCL11
NM_005409.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

Publications

2 publications found

Variant links:

Genes affected

CXCL11 (HGNC:10638): (C-X-C motif chemokine ligand 11) Chemokines are a group of small (approximately 8 to 14 kD), mostly basic, structurally related molecules that regulate cell trafficking of various types of leukocytes through interactions with a subset of 7-transmembrane, G protein-coupled receptors. Chemokines also play fundamental roles in the development, homeostasis, and function of the immune system, and they have effects on cells of the central nervous system as well as on endothelial cells involved in angiogenesis or angiostasis. Chemokines are divided into 2 major subfamilies, CXC and CC. This antimicrobial gene is a CXC member of the chemokine superfamily. Its encoded protein induces a chemotactic response in activated T-cells and is the dominant ligand for CXC receptor-3. The gene encoding this protein contains 4 exons and at least three polyadenylation signals which might reflect cell-specific regulation of expression. IFN-gamma is a potent inducer of transcription of this gene. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2014]

CXCL11 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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17767838).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005409.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CXCL11	NM_005409.5	MANE Select	c.215A>G	p.Gln72Arg	missense	Exon 3 of 4	NP_005400.1	O14625
CXCL11	NM_001302123.2		c.215A>G	p.Gln72Arg	missense	Exon 3 of 4	NP_001289052.1
ART3	NM_001130017.3		c.-10+23773T>C		intron	N/A	NP_001123489.1	Q13508-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CXCL11	ENST00000306621.8	TSL:1 MANE Select	c.215A>G	p.Gln72Arg	missense	Exon 3 of 4	ENSP00000306884.3	O14625
ART3	ENST00000341029.9	TSL:1	c.-10+23773T>C		intron	N/A	ENSP00000343843.5	Q13508-2
ART3	ENST00000513122.5	TSL:1	c.-124-22897T>C		intron	N/A	ENSP00000422287.1	E7ESB3

Frequencies

GnomAD3 genomes

AF:

0.000192

AC:

AN:

151308

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000371

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000187

AC:

AN:

251172

AF XY:

0.000214

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000282

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000208

AC:

301

AN:

1450164

Hom.:

Cov.:

AF XY:

0.000238

AC XY:

172

AN XY:

721394

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33436

American (AMR)

AF:

0.000112

AC:

AN:

44594

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26090

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.000467

AC:

AN:

85742

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.000880

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.000211

AC:

232

AN:

1101710

Other (OTH)

AF:

0.000317

AC:

AN:

59846

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000192

AC:

AN:

151308

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

73912

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41312

American (AMR)

AF:

0.0000658

AC:

AN:

15190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000416

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.000371

AC:

AN:

67464

Other (OTH)

AF:

0.00

AC:

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00308

Hom.:

Bravo

AF:

0.000170

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000173

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.51

M_CAP

Benign

0.081

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.96

PhyloP100

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.7

REVEL

Benign

0.10

Sift

Benign

0.14

Sift4G

Benign

0.26

Polyphen

0.77

Vest4

0.26

MVP

0.74

MPC

0.10

ClinPred

0.13

GERP RS

5.1

Varity_R

0.14

gMVP

0.46

Mutation Taster

=94/6

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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