dbSNP rs35795399: CXCL10:c.*406A>G (chr4-76021524-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.546

Publications

6 publications found

Variant links:

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]

CXCL10 links:

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]

ART3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL10	NM_001565.4 link	c.*406A>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000306602.3	NP_001556.2	P02778

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL10	ENST00000306602.3 link	c.*406A>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_001565.4	ENSP00000305651.1		P02778

Frequencies

GnomAD3 genomes

AF:

0.0145

AC:

2203

AN:

152212

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.0168

AC XY:

175

AN XY:

10418

show subpopulations

African (AFR)

AF:

0.00646

AC:

AN:

774

American (AMR)

AF:

0.00949

AC:

AN:

948

Ashkenazi Jewish (ASJ)

AF:

0.00591

AC:

AN:

846

East Asian (EAS)

AF:

0.00

AC:

AN:

1086

South Asian (SAS)

AF:

0.00256

AC:

AN:

390

European-Finnish (FIN)

AF:

0.0341

AC:

AN:

1202

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0201

AC:

275

AN:

13652

Other (OTH)

AF:

0.0125

AC:

AN:

1276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0145

AC:

2202

AN:

152330

Hom.:

Cov.:

AF XY:

0.0143

AC XY:

1068

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00356

AC:

148

AN:

41578

American (AMR)

AF:

0.00608

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00922

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00890

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0337

AC:

358

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0222

AC:

1510

AN:

68034

Other (OTH)

AF:

0.00804

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

110

220

330

440

550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0165

Hom.:

Bravo

AF:

0.0116

Asia WGS

AF:

0.00491

AC:

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

(source)

DANN

Benign

0.61

PhyloP100

-0.55

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over