4-76021524-T-C

Variant names:

• chr4-76021524-T-C
• rs35795399
• NM_001565.4:c.*406A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2202 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001565.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL10	NM_001565.4	MANE Select	c.*406A>G		3_prime_UTR	Exon 4 of 4	NP_001556.2
	CXCL10	NR_168520.1		n.642A>G		non_coding_transcript_exon	Exon 3 of 3
	ART3	NM_001130017.3		c.-10+10204T>C		intron	N/A	NP_001123489.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL10	ENST00000306602.3	TSL:1 MANE Select	c.*406A>G		3_prime_UTR	Exon 4 of 4	ENSP00000305651.1
	ART3	ENST00000341029.9	TSL:1	c.-10+10204T>C		intron	N/A	ENSP00000343843.5
	ART3	ENST00000513122.5	TSL:1	c.-125+10204T>C		intron	N/A	ENSP00000422287.1

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

African (AFR) AF: 0.00646 AC: 5 AN: 774

American (AMR) AF: 0.00949 AC: 9 AN: 948

Ashkenazi Jewish (ASJ) AF: 0.00591 AC: 5 AN: 846

East Asian (EAS) AF: 0.00 AC: 0 AN: 1086

South Asian (SAS) AF: 0.00256 AC: 1 AN: 390

European-Finnish (FIN) AF: 0.0341 AC: 41 AN: 1202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 76

European-Non Finnish (NFE) AF: 0.0201 AC: 275 AN: 13652

Other (OTH) AF: 0.0125 AC: 16 AN: 1276

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

African (AFR) AF: 0.00356 AC: 148 AN: 41578

American (AMR) AF: 0.00608 AC: 93 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00890 AC: 43 AN: 4830

European-Finnish (FIN) AF: 0.0337 AC: 358 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0222 AC: 1510 AN: 68034

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.0165 Hom.: 39

Bravo AF: 0.0116

Asia WGS AF: 0.00491 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.62
DANN	Benign	0.61
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs35795399; hg19: chr4-76942677;