Genetic Variant IL10:c.*518G>A (chr1-206768118-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000572.3(IL10):c.*518G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 217,102 control chromosomes in the GnomAD database, including 141 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 0.022 ( 131 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 10 hom. )

Consequence

IL10
NM_000572.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0260

Publications

4 publications found

Variant links:

Genes affected

IL10 (HGNC:5962): (interleukin 10) The protein encoded by this gene is a cytokine produced primarily by monocytes and to a lesser extent by lymphocytes. This cytokine has pleiotropic effects in immunoregulation and inflammation. It down-regulates the expression of Th1 cytokines, MHC class II Ags, and costimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production. This cytokine can block NF-kappa B activity, and is involved in the regulation of the JAK-STAT signaling pathway. Knockout studies in mice suggested the function of this cytokine as an essential immunoregulator in the intestinal tract. Mutations in this gene are associated with an increased susceptibility to HIV-1 infection and rheumatoid arthritis. [provided by RefSeq, May 2020]

IL10 Gene-Disease associations (from GenCC):

IL10-related early-onset inflammatory bowel disease
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics
systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

IL10 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=-0.69).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
IL10	NM_000572.3 link	c.*518G>A	3_prime_UTR_variant	Exon 5 of 5	ENST00000423557.1	NP_000563.1
IL10	NR_168466.1 link	n.1352G>A	non_coding_transcript_exon_variant	Exon 6 of 6
IL10	NR_168467.1 link	n.882G>A	non_coding_transcript_exon_variant	Exon 3 of 3
IL10	NM_001382624.1 link	c.*518G>A	3_prime_UTR_variant	Exon 3 of 3		NP_001369553.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10	ENST00000423557.1 link	c.*518G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_000572.3	ENSP00000412237.1

Frequencies

GnomAD3 genomes

AF:

0.0224

AC:

3408

AN:

152114

Hom.:

131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0790

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00556

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.0148

GnomAD4 exome

AF:

0.00355

AC:

230

AN:

64870

Hom.:

Cov.:

AF XY:

0.00341

AC XY:

106

AN XY:

31072

show subpopulations

African (AFR)

AF:

0.0707

AC:

179

AN:

2532

American (AMR)

AF:

0.00418

AC:

AN:

2632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3632

East Asian (EAS)

AF:

0.00

AC:

AN:

9050

South Asian (SAS)

AF:

0.00

AC:

AN:

1396

European-Finnish (FIN)

AF:

0.00

AC:

AN:

246

Middle Eastern (MID)

AF:

0.00

AC:

AN:

402

European-Non Finnish (NFE)

AF:

0.000150

AC:

AN:

39950

Other (OTH)

AF:

0.00676

AC:

AN:

5030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0224

AC:

3417

AN:

152232

Hom.:

131

Cov.:

AF XY:

0.0214

AC XY:

1593

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0790

AC:

3280

AN:

41530

American (AMR)

AF:

0.00556

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000416

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

68010

Other (OTH)

AF:

0.0147

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

157

313

470

626

783

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0135

Hom.:

Bravo

AF:

0.0260

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.1

(source)

DANN

Benign

0.77

PhyloP100

0.026

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