Menu
GeneBe

4-76022401-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001565.4(CXCL10):c.243C>A(p.Ala81=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000975 in 1,613,576 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 8 hom., cov: 32)
Exomes 𝑓: 0.00054 ( 9 hom. )

Consequence

CXCL10
NM_001565.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.290
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
Variant 4-76022401-G-T is Benign according to our data. Variant chr4-76022401-G-T is described in ClinVar as [Benign]. Clinvar id is 731714.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.29 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00517 (787/152252) while in subpopulation AFR AF= 0.0176 (730/41544). AF 95% confidence interval is 0.0165. There are 8 homozygotes in gnomad4. There are 357 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
High AC in GnomAd at 789 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CXCL10NM_001565.4 linkuse as main transcriptc.243C>A p.Ala81= synonymous_variant 3/4 ENST00000306602.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CXCL10ENST00000306602.3 linkuse as main transcriptc.243C>A p.Ala81= synonymous_variant 3/41 NM_001565.4 P1

Frequencies

GnomAD3 genomes
AF:
0.00519
AC:
789
AN:
152134
Hom.:
8
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0177
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00249
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000622
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00478
GnomAD3 exomes
AF:
0.00144
AC:
358
AN:
249214
Hom.:
5
AF XY:
0.00105
AC XY:
142
AN XY:
135244
show subpopulations
Gnomad AFR exome
AF:
0.0202
Gnomad AMR exome
AF:
0.00116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000353
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000539
AC:
787
AN:
1461324
Hom.:
9
Cov.:
31
AF XY:
0.000469
AC XY:
341
AN XY:
726968
show subpopulations
Gnomad4 AFR exome
AF:
0.0192
Gnomad4 AMR exome
AF:
0.00125
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.00114
GnomAD4 genome
AF:
0.00517
AC:
787
AN:
152252
Hom.:
8
Cov.:
32
AF XY:
0.00479
AC XY:
357
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.0176
Gnomad4 AMR
AF:
0.00249
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000622
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00473
Alfa
AF:
0.00289
Hom.:
1
Bravo
AF:
0.00602
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 31, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
Cadd
Benign
4.1
Dann
Benign
0.60

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: rs139813823; hg19: chr4-76943554; API