4-76021147-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001565.4(CXCL10):c.*783T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 152,160 control chromosomes in the GnomAD database, including 29,545 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (29542 hom., cov: 32)
  • Exomes 𝑓: 0.38 (3 hom.)
• Consequence: CXCL10 NM_001565.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCL10	NM_001565.4	c.*783T>C		3_prime_UTR_variant	4/4	ENST00000306602.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCL10	ENST00000306602.3	c.*783T>C		3_prime_UTR_variant	4/4	1	NM_001565.4	P1

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92926 AN: 151974 Hom.: 29490 Cov.: 32

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.620

GnomAD4 exome AF: 0.382 AC: 26 AN: 68 Hom.: 3 Cov.: 0 AF XY: 0.333 AC XY: 12 AN XY: 36

Gnomad4 FIN exome AF: 0.382

GnomAD4 genome AF: 0.612 AC: 93042 AN: 152092 Hom.: 29542 Cov.: 32 AF XY: 0.612 AC XY: 45481 AN XY: 74350

Gnomad4 AFR AF: 0.705

Gnomad4 AMR AF: 0.717

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.939

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.621

Alfa AF: 0.560 Hom.: 37965

Bravo AF: 0.640

Asia WGS AF: 0.720 AC: 2500 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.3
Dann	Benign	0.77

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: rs8878; hg19: chr4-76942300;