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

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 links:

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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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IL10	NM_000572.3 link	c.444+58A>G	intron_variant	Intron 4 of 4	ENST00000423557.1	NP_000563.1	P22301Q6FGW4
IL10	NM_001382624.1 link	c.189+58A>G	intron_variant	Intron 2 of 2		NP_001369553.1
IL10	NR_168466.1 link	n.741+58A>G	intron_variant	Intron 5 of 5
IL10	NR_168467.1 link	n.271+58A>G	intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10	ENST00000423557.1 link	c.444+58A>G		intron_variant	Intron 4 of 4	1	NM_000572.3	ENSP00000412237.1		P22301

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

Gnomad4 AFR exome

AF:

0.000473

AC:

AN:

27510

Gnomad4 AMR exome

AF:

0.0384

AC:

1702

AN:

44354

Gnomad4 ASJ exome

AF:

0.00326

AC:

AN:

24260

Gnomad4 EAS exome

AF:

0.0559

AC:

2143

AN:

38306

Gnomad4 SAS exome

AF:

0.00199

AC:

160

AN:

80264

Gnomad4 FIN exome

AF:

0.0109

AC:

583

AN:

53280

Gnomad4 NFE exome

AF:

0.000554

AC:

463

AN:

835720

Gnomad4 Remaining exome

AF:

0.00435

AC:

219

AN:

50380

Heterozygous variant carriers

330

660

991

1321

1651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Gnomad4 AFR

AF:

0.000722

AC:

0.000722439

AN:

0.000722439

Gnomad4 AMR

AF:

0.0250

AC:

0.0249673

AN:

0.0249673

Gnomad4 ASJ

AF:

0.00288

AC:

0.00288018

AN:

0.00288018

Gnomad4 EAS

AF:

0.0344

AC:

0.0343762

AN:

0.0343762

Gnomad4 SAS

AF:

0.00311

AC:

0.00310945

AN:

0.00310945

Gnomad4 FIN

AF:

0.0105

AC:

0.0104559

AN:

0.0104559

Gnomad4 NFE

AF:

0.000691

AC:

0.000691115

AN:

0.000691115

Gnomad4 OTH

AF:

0.00615

AC:

0.00614948

AN:

0.00614948

Heterozygous variant carriers

109

146

182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.89

DANN

Benign

0.61

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over