4-76006220-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002416.3(CXCL9):ā€‹c.119C>Gā€‹(p.Thr40Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 1,613,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.00080 ( 0 hom., cov: 32)
Exomes š‘“: 0.000085 ( 0 hom. )

Consequence

CXCL9
NM_002416.3 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.04
Variant links:
Genes affected
CXCL9 (HGNC:7098): (C-X-C motif chemokine ligand 9) This antimicrobial gene is part of a chemokine superfamily that encodes secreted proteins involved in immunoregulatory and inflammatory processes. The protein encoded is thought to be involved in T cell trafficking. The encoded protein binds to C-X-C motif chemokine 3 and is a chemoattractant for lymphocytes but not for neutrophils. [provided by RefSeq, Aug 2020]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.010850817).
BP6
Variant 4-76006220-G-C is Benign according to our data. Variant chr4-76006220-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 737558.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CXCL9NM_002416.3 linkc.119C>G p.Thr40Ser missense_variant 2/4 ENST00000264888.6 NP_002407.1 Q07325

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CXCL9ENST00000264888.6 linkc.119C>G p.Thr40Ser missense_variant 2/41 NM_002416.3 ENSP00000354901.4 Q07325

Frequencies

GnomAD3 genomes
AF:
0.000802
AC:
122
AN:
152200
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00287
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.000207
AC:
52
AN:
251456
Hom.:
1
AF XY:
0.000155
AC XY:
21
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.00301
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.0000848
AC:
124
AN:
1461520
Hom.:
0
Cov.:
30
AF XY:
0.0000839
AC XY:
61
AN XY:
727082
show subpopulations
Gnomad4 AFR exome
AF:
0.00335
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.000132
GnomAD4 genome
AF:
0.000801
AC:
122
AN:
152318
Hom.:
0
Cov.:
32
AF XY:
0.000685
AC XY:
51
AN XY:
74502
show subpopulations
Gnomad4 AFR
AF:
0.00286
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.000763
Hom.:
0
Bravo
AF:
0.000948
ESP6500AA
AF:
0.00409
AC:
18
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000296
AC:
36

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMar 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.098
BayesDel_addAF
Benign
-0.68
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
0.0020
DANN
Benign
0.69
DEOGEN2
Benign
0.068
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.32
T
M_CAP
Benign
0.0074
T
MetaRNN
Benign
0.011
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
1.4
L
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.88
N
REVEL
Benign
0.023
Sift
Benign
0.35
T
Sift4G
Benign
0.73
T
Polyphen
0.027
B
Vest4
0.23
MutPred
0.32
Gain of disorder (P = 0.0351);
MVP
0.072
MPC
0.35
ClinPred
0.026
T
GERP RS
-11
Varity_R
0.035
gMVP
0.16

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs145442311; hg19: chr4-76927373; API