chr1-206768519-A-G

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

2

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]

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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 HGVSp Effect #exon/exons MANE Protein UniProt
IL10NM_000572.3 linkuse as main transcriptc.*117T>C 3_prime_UTR_variant 5/5 ENST00000423557.1 NP_000563.1
IL10NM_001382624.1 linkuse as main transcriptc.*117T>C 3_prime_UTR_variant 3/3 NP_001369553.1
IL10NR_168466.1 linkuse as main transcriptn.951T>C non_coding_transcript_exon_variant 6/6
IL10NR_168467.1 linkuse as main transcriptn.481T>C non_coding_transcript_exon_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IL10ENST00000423557.1 linkuse as main transcriptc.*117T>C 3_prime_UTR_variant 5/51 NM_000572.3 ENSP00000412237 P1

Frequencies

GnomAD3 genomes
AF:
0.417
AC:
63370
AN:
151816
Hom.:
13979
Cov.:
31
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.:
4
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.:
31
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
Benign, criteria provided, single submitterclinical testingUnidad de Genómica Garrahan, Hospital de Pediatría GarrahanNov 12, 2023This 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.

Other links and lift over

dbSNP: rs3024496; hg19: chr1-206941864; COSMIC: COSV65594494; COSMIC: COSV65594494; API