Genetic Variant NM_000572.3:c.379-474C>A (chr1-206770368-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000572.3(IL10):c.379-474C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 151,980 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IL10
NM_000572.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.38

Publications

58 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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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
IL10	NM_000572.3	MANE Select	c.379-474C>A	intron	N/A	NP_000563.1
IL10	NM_001382624.1		c.124-474C>A	intron	N/A	NP_001369553.1
IL10	NR_168466.1		n.438-49C>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IL10	ENST00000423557.1	TSL:1 MANE Select	c.379-474C>A	intron	N/A	ENSP00000412237.1
IL10	ENST00000659065.2		c.262-474C>A	intron	N/A	ENSP00000499588.1
IL10	ENST00000659642.2		c.262-474C>A	intron	N/A	ENSP00000499509.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

120926

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

64008

African (AFR)

AF:

0.00

AC:

AN:

4276

American (AMR)

AF:

0.00

AC:

AN:

5464

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3050

East Asian (EAS)

AF:

0.00

AC:

AN:

6230

South Asian (SAS)

AF:

0.00

AC:

AN:

19264

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

476

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

70760

Other (OTH)

AF:

0.00

AC:

AN:

6300

GnomAD4 genome

AF:

0.0000197

AC:

AN:

151980

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74216

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41356

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67992

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

966

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.019

(source)

DANN

Benign

0.14

PhyloP100

-2.4

PromoterAI

-0.010

Neutral

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over