NM_001565.4:c.*140G>C

Variant names:

• chr4-76021790-C-G
• rs3921
• NM_001565.4:c.*140G>C

Variant summary

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

The NM_001565.4(CXCL10):​c.*140G>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 0.575 in 808,708 control chromosomes in the GnomAD database, including 139,825 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 (29621 hom., cov: 31)
  • Exomes 𝑓: 0.57 (110204 hom.)
• Consequence: CXCL10 NM_001565.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.562

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 rank	MANE	Protein	UniProt
CXCL10	NM_001565.4	c.*140G>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000306602.3	NP_001556.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL10	ENST00000306602	c.*140G>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_001565.4	ENSP00000305651.1

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92983 AN: 151854 Hom.: 29564 Cov.: 31

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.623

GnomAD4 exome AF: 0.566 AC: 371661 AN: 656736 Hom.: 110204 Cov.: 8 AF XY: 0.562 AC XY: 195616 AN XY: 347974

Gnomad4 AFR exome AF: 0.710

Gnomad4 AMR exome AF: 0.806

Gnomad4 ASJ exome AF: 0.616

Gnomad4 EAS exome AF: 0.935

Gnomad4 SAS exome AF: 0.527

Gnomad4 FIN exome AF: 0.478

Gnomad4 NFE exome AF: 0.518

Gnomad4 OTH exome AF: 0.576

GnomAD4 genome AF: 0.613 AC: 93108 AN: 151972 Hom.: 29621 Cov.: 31 AF XY: 0.612 AC XY: 45490 AN XY: 74272

Gnomad4 AFR AF: 0.708

Gnomad4 AMR AF: 0.718

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.939

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.624

Alfa AF: 0.451 Hom.: 1274

Bravo AF: 0.641

Asia WGS AF: 0.721 AC: 2506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.26

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: rs3921; hg19: chr4-76942943;