4-76021524-T-C

Position:

• chr4-76021524-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001565.4(CXCL10):​c.*406A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 172,580 control chromosomes in the GnomAD database, including 34 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 0.014 (29 hom., cov: 33)
  • Exomes 𝑓: 0.017 (5 hom.)
• Consequence: CXCL10 NM_001565.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546

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).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0145 (2202/152330) while in subpopulation NFE AF= 0.0222 (1510/68034). AF 95% confidence interval is 0.0213. There are 29 homozygotes in gnomad4. There are 1068 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2202 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCL10	NM_001565.4	c.*406A>G		3_prime_UTR_variant	4/4	ENST00000306602.3	NP_001556.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCL10	ENST00000306602.3	c.*406A>G		3_prime_UTR_variant	4/4	1	NM_001565.4	ENSP00000305651	P1

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2203 AN: 152212 Hom.: 29 Cov.: 33

Gnomad AFR AF: 0.00357

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00608

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00910

Gnomad FIN AF: 0.0337

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0222

Gnomad OTH AF: 0.00813

GnomAD4 exome AF: 0.0174 AC: 352 AN: 20250 Hom.: 5 Cov.: 0 AF XY: 0.0168 AC XY: 175 AN XY: 10418

Gnomad4 AFR exome AF: 0.00646

Gnomad4 AMR exome AF: 0.00949

Gnomad4 ASJ exome AF: 0.00591

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00256

Gnomad4 FIN exome AF: 0.0341

Gnomad4 NFE exome AF: 0.0201

Gnomad4 OTH exome AF: 0.0125

GnomAD4 genome AF: 0.0145 AC: 2202 AN: 152330 Hom.: 29 Cov.: 33 AF XY: 0.0143 AC XY: 1068 AN XY: 74488

Gnomad4 AFR AF: 0.00356

Gnomad4 AMR AF: 0.00608

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00890

Gnomad4 FIN AF: 0.0337

Gnomad4 NFE AF: 0.0222

Gnomad4 OTH AF: 0.00804

Alfa AF: 0.0171 Hom.: 28

Bravo AF: 0.0116

Asia WGS AF: 0.00491 AC: 18 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	0.62
DANN	Benign	0.61

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: rs35795399; hg19: chr4-76942677;