dbSNP rs3024510: IL10:c.*345A>T (chr1-206768291-T-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000572.3(IL10):c.*345A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0029 in 317,028 control chromosomes in the GnomAD database, including 2 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 0.0029 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 1 hom. )

Consequence

IL10
NM_000572.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0440

Publications

6 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IL10	NM_000572.3 link	c.*345A>T	3_prime_UTR_variant	Exon 5 of 5	ENST00000423557.1	NP_000563.1	P22301Q6FGW4
IL10	NR_168466.1 link	n.1179A>T	non_coding_transcript_exon_variant	Exon 6 of 6
IL10	NR_168467.1 link	n.709A>T	non_coding_transcript_exon_variant	Exon 3 of 3
IL10	NM_001382624.1 link	c.*345A>T	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.*345A>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_000572.3	ENSP00000412237.1		P22301

Frequencies

GnomAD3 genomes

AF:

0.00295

AC:

448

AN:

151970

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000679

Gnomad AMI

AF:

0.0418

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00375

Gnomad OTH

AF:

0.00383

GnomAD4 exome

AF:

0.00286

AC:

471

AN:

164940

Hom.:

Cov.:

AF XY:

0.00290

AC XY:

243

AN XY:

83836

show subpopulations

African (AFR)

AF:

0.000198

AC:

AN:

5050

American (AMR)

AF:

0.00274

AC:

AN:

6214

Ashkenazi Jewish (ASJ)

AF:

0.00233

AC:

AN:

6856

East Asian (EAS)

AF:

0.00

AC:

AN:

14466

South Asian (SAS)

AF:

0.00194

AC:

AN:

15492

European-Finnish (FIN)

AF:

0.00108

AC:

AN:

3698

Middle Eastern (MID)

AF:

0.00397

AC:

AN:

756

European-Non Finnish (NFE)

AF:

0.00361

AC:

367

AN:

101680

Other (OTH)

AF:

0.00308

AC:

AN:

10728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

109

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:

0.00295

AC:

448

AN:

152088

Hom.:

Cov.:

AF XY:

0.00268

AC XY:

199

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.000677

AC:

AN:

41344

American (AMR)

AF:

0.00464

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00290

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00198

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00375

AC:

255

AN:

68030

Other (OTH)

AF:

0.00379

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

100

125

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:

0.00130

Hom.:

Bravo

AF:

0.00349

Asia WGS

AF:

0.00231

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

1.6

(source)

DANN

Benign

0.67

PhyloP100

-0.044

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