rs11548618

chr4-76022794-G-Achr4-76022794-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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 (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0067 (59 hom.)
• Consequence: CXCL10 NM_001565.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.79

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]

ACMG classification

Verdict is Benign. Variant got -10 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_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 839 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCL10	NM_001565.4	c.85C>T	p.Arg29Cys	missense_variant	2/4	ENST00000306602.3

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00551 AC: 839 AN: 152178 Hom.: 5 Cov.: 32

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.: 6 AF XY: 0.00594 AC XY: 797 AN XY: 134286

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.: 59 Cov.: 31 AF XY: 0.00656 AC XY: 4763 AN XY: 726070

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.: 6 Cov.: 32 AF XY: 0.00572 AC XY: 426 AN XY: 74468

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.: 13

Bravo AF: 0.00445

TwinsUK AF: 0.00971 AC: 36

ALSPAC AF: 0.00545 AC: 21

ESP6500AA AF: 0.00129 AC: 5

ESP6500EA AF: 0.00736 AC: 61

ExAC AF: 0.00611 AC: 739

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.00829

EpiControl AF: 0.00682

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Uncertain	0.060
Cadd	Pathogenic	30
Dann	Pathogenic	1.0
DEOGEN2	Pathogenic	0.89	D
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.74	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-7.3	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.82
MVP		0.63
MPC		0.56
ClinPred		0.057	T
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

Other links and lift over

dbSNP: rs11548618; hg19: chr4-76943947; COSMIC: COSV60660883;