Variant 1-206768519-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000572.3(IL10):c.*117T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 695,764 control chromosomes in the GnomAD database, including 64,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.42 ( 14000 hom., cov: 31)

Exomes 𝑓: 0.41 ( 50042 hom. )

Consequence

IL10
NM_000572.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.453

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 1-206768519-A-G is Benign according to our data. Variant chr1-206768519-A-G is described in ClinVar as [Benign]. Clinvar id is 2628225.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-206768519-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IL10	NM_000572.3 link	c.*117T>C	3_prime_UTR_variant	Exon 5 of 5	ENST00000423557.1	NP_000563.1	P22301Q6FGW4
IL10	NM_001382624.1 link	c.*117T>C	3_prime_UTR_variant	Exon 3 of 3		NP_001369553.1
IL10	NR_168466.1 link	n.951T>C	non_coding_transcript_exon_variant	Exon 6 of 6
IL10	NR_168467.1 link	n.481T>C	non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10	ENST00000423557 link	c.*117T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_000572.3	ENSP00000412237.1		P22301

Frequencies

GnomAD3 genomes

AF:

0.417

AC:

63370

AN:

151816

Hom.:

13979

Cov.:

show subpopulations

Gnomad AFR

AF:

0.404

Gnomad AMI

AF:

0.442

Gnomad AMR

AF:

0.305

Gnomad ASJ

AF:

0.406

Gnomad EAS

AF:

0.0314

Gnomad SAS

AF:

0.244

Gnomad FIN

AF:

0.473

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.485

Gnomad OTH

AF:

0.390

GnomAD4 exome

AF:

0.408

AC:

221827

AN:

543830

Hom.:

50042

Cov.:

AF XY:

0.401

AC XY:

118071

AN XY:

294534

show subpopulations

Gnomad4 AFR exome

AF:

0.409

Gnomad4 AMR exome

AF:

0.279

Gnomad4 ASJ exome

AF:

0.425

Gnomad4 EAS exome

AF:

0.0229

Gnomad4 SAS exome

AF:

0.272

Gnomad4 FIN exome

AF:

0.455

Gnomad4 NFE exome

AF:

0.480

Gnomad4 OTH exome

AF:

0.417

GnomAD4 genome

AF:

0.418

AC:

63439

AN:

151934

Hom.:

14000

Cov.:

AF XY:

0.410

AC XY:

30441

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.405

Gnomad4 AMR

AF:

0.305

Gnomad4 ASJ

AF:

0.406

Gnomad4 EAS

AF:

0.0311

Gnomad4 SAS

AF:

0.243

Gnomad4 FIN

AF:

0.473

Gnomad4 NFE

AF:

0.485

Gnomad4 OTH

AF:

0.393

Alfa

AF:

0.452

Hom.:

17315

Bravo

AF:

0.406

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 34% of patients studied by a panel of primary immunodeficiencies. Number of patients: 33. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.7

DANN

Benign

0.67

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over