Variant 4-76022794-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000306602.3(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 (★★).

Frequency

Genomes: 𝑓 0.0055 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0067 ( 59 hom. )

Consequence

CXCL10
ENST00000306602.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.79

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 made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
CXCL10	NM_001565.4 linkuse as main transcript	c.85C>T	p.Arg29Cys	missense_variant	2/4	ENST00000306602.3	NP_001556.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCL10	ENST00000306602.3 linkuse as main transcript	c.85C>T	p.Arg29Cys	missense_variant	2/4	1	NM_001565.4	ENSP00000305651	P1

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

GnomAD3 exomes

AF:

0.00582

AC:

1438

AN:

247090

Hom.:

AF XY:

0.00594

AC XY:

797

AN XY:

134286

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 SAS exome

AF:

0.00124

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

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.00344

Gnomad4 ASJ exome

AF:

0.00191

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00145

Gnomad4 FIN exome

AF:

0.0113

Gnomad4 NFE exome

AF:

0.00761

Gnomad4 OTH exome

AF:

0.00578

GnomAD4 genome

AF:

0.00552

AC:

841

AN:

152296

Hom.:

Cov.:

AF XY:

0.00572

AC XY:

426

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0106

Gnomad4 NFE

AF:

0.00860

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00796

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 07, 2018	- -

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

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

MutationTaster

Benign

1.0

D;D

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over