Genetic Variant IL10:c.444+58A>G (chr1-206769771-T-C) – 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.444+58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00469 in 1,310,722 control chromosomes in the GnomAD database, including 140 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 0.0052 ( 13 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 127 hom. )

Consequence

IL10
NM_000572.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.00

Publications

1 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: MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, ClinGen, Orphanet
systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

IL10 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000572.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.82).

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.054 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000572.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL10	NM_000572.3	MANE Select	c.444+58A>G	intron	N/A	NP_000563.1	P22301
IL10	NM_001382624.1		c.189+58A>G	intron	N/A	NP_001369553.1	A0A286YEX3
IL10	NR_168466.1		n.741+58A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL10	ENST00000423557.1	TSL:1 MANE Select	c.444+58A>G	intron	N/A	ENSP00000412237.1	P22301
IL10	ENST00000659065.2		c.327+58A>G	intron	N/A	ENSP00000499588.1	A0A590UK12
IL10	ENST00000659642.2		c.327+58A>G	intron	N/A	ENSP00000499509.1	A0A590UK12

Frequencies

GnomAD3 genomes

AF:

0.00514

AC:

782

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0248

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.0343

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0105

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.00621

GnomAD4 exome

AF:

0.00463

AC:

5367

AN:

1158480

Hom.:

127

Cov.:

AF XY:

0.00432

AC XY:

2554

AN XY:

591190

show subpopulations

African (AFR)

AF:

0.000473

AC:

AN:

27510

American (AMR)

AF:

0.0384

AC:

1702

AN:

44354

Ashkenazi Jewish (ASJ)

AF:

0.00326

AC:

AN:

24260

East Asian (EAS)

AF:

0.0559

AC:

2143

AN:

38306

South Asian (SAS)

AF:

0.00199

AC:

160

AN:

80264

European-Finnish (FIN)

AF:

0.0109

AC:

583

AN:

53280

Middle Eastern (MID)

AF:

0.00113

AC:

AN:

4406

European-Non Finnish (NFE)

AF:

0.000554

AC:

463

AN:

835720

Other (OTH)

AF:

0.00435

AC:

219

AN:

50380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

330

660

991

1321

1651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<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:

0.00516

AC:

786

AN:

152242

Hom.:

Cov.:

AF XY:

0.00646

AC XY:

481

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.000722

AC:

AN:

41526

American (AMR)

AF:

0.0250

AC:

382

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3472

East Asian (EAS)

AF:

0.0344

AC:

178

AN:

5178

South Asian (SAS)

AF:

0.00311

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0105

AC:

111

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000691

AC:

AN:

68006

Other (OTH)

AF:

0.00615

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

109

146

182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00418

Hom.:

Bravo

AF:

0.00674

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.89

(source)

DANN

Benign

0.61

PhyloP100

-2.0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over