4-76022143-A-C

Position:

• chr4-76022143-A-C

Variant summary

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

The NM_001565.4(CXCL10):​c.279-195T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 152,016 control chromosomes in the GnomAD database, including 29,518 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 (29518 hom., cov: 32)
• Consequence: CXCL10 NM_001565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.419

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=-0.82).
• 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	Protein	UniProt
CXCL10	NM_001565.4	c.279-195T>G		intron_variant		ENST00000306602.3	NP_001556.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCL10	ENST00000306602.3	c.279-195T>G		intron_variant		1	NM_001565.4	ENSP00000305651	P1

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92867 AN: 151894 Hom.: 29466 Cov.: 32

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.619

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.612 AC: 92985 AN: 152016 Hom.: 29518 Cov.: 32 AF XY: 0.611 AC XY: 45431 AN XY: 74314

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: 0.471

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.620

Alfa AF: 0.421 Hom.: 1041

Bravo AF: 0.640

Asia WGS AF: 0.721 AC: 2505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.6
DANN	Benign	0.76

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: rs4859587; hg19: chr4-76943296;