1-206773062-T-G

Position:

• chr1-206773062-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153758.5(IL19):​c.-149+1984T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,058 control chromosomes in the GnomAD database, including 36,716 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.69 (36716 hom., cov: 31)
• Consequence: IL19 NM_153758.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:2
• Conservation: PhyloP100: 0.260

Genes affected

IL19 (HGNC:5990): (interleukin 19) The protein encoded by this gene is a cytokine that belongs to the IL10 cytokine subfamily. This cytokine is found to be preferentially expressed in monocytes. It can bind the IL20 receptor complex and lead to the activation of the signal transducer and activator of transcription 3 (STAT3). A similar cytokine in mouse is reported to up-regulate the expression of IL6 and TNF-alpha and induce apoptosis, which suggests a role of this cytokine in inflammatory responses. Alternatively spliced transcript variants encoding the distinct isoforms have been described. [provided by RefSeq, Jul 2008]

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-206773062-T-G is Benign according to our data. Variant chr1-206773062-T-G is described in ClinVar as [Benign]. Clinvar id is 16873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL19	NM_153758.5	c.-149+1984T>G		intron_variant		ENST00000659997.3	NP_715639.2
IL19	NM_001393490.1	c.-149+2232T>G		intron_variant			NP_001380419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL19	ENST00000659997.3	c.-149+1984T>G		intron_variant			NM_153758.5	ENSP00000499459	P1

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104271 AN: 151940 Hom.: 36691 Cov.: 31

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.678

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.686 AC: 104356 AN: 152058 Hom.: 36716 Cov.: 31 AF XY: 0.682 AC XY: 50730 AN XY: 74346

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.674

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.776

Gnomad4 NFE AF: 0.768

Gnomad4 OTH AF: 0.680

Alfa AF: 0.706 Hom.: 6316

Bravo AF: 0.674

Asia WGS AF: 0.488 AC: 1701 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3 Other:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Graft-versus-host disease, resistance to Benign:1

protective, no assertion criteria provided

literature only

OMIM

Dec 04, 2003

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Inflammatory bowel disease Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

Susceptibility to HIV infection Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Dec 04, 2003

- -

Cholangiocarcinoma Other:1

other, no assertion criteria provided

research

Department of Surgery, Campus Charité Mitte Campus Virchow-klinikum, Charite-Universitaetsmedizin Berlin

Dec 10, 2022

No association with disease-free or overall survival after resection of intrahepatic Cholangiocarcinoma No association with disease-free or overall survival

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.0
DANN	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1800872; hg19: chr1-206946407;