rs4803219

Variant names:

• chr19-39245279-C-T
• rs4803219
• ENST00000613087.5:c.-202G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000613087.5(IFNL3):​c.-202G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 584,244 control chromosomes in the GnomAD database, including 21,237 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 0.28 (5609 hom., cov: 22)
  • Exomes 𝑓: 0.26 (15628 hom.)
• Consequence: IFNL3 ENST00000613087.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49
• Publications: 29 publications found

Genes affected

IFNL3 (HGNC:18365): (interferon lambda 3) This gene encodes a cytokine distantly related to type I interferons and the IL-10 family. This gene, interleukin 28A (IL28A), and interleukin 29 (IL29) are three closely related cytokine genes that form a cytokine gene cluster on a chromosomal region mapped to 19q13. Expression of the cytokines encoded by the three genes can be induced by viral infection. All three cytokines have been shown to interact with a heterodimeric class II cytokine receptor that consists of interleukin 10 receptor, beta (IL10RB) and interleukin 28 receptor, alpha (IL28RA). [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNL3	NM_001346937.2	c.-202G>A		upstream_gene_variant			NP_001333866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNL3	ENST00000613087.5	c.-202G>A		upstream_gene_variant		1		ENSP00000481633.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 40163 AN: 145134 Hom.: 5605 Cov.: 22

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.0682

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.284

GnomAD4 exome AF: 0.258 AC: 113229 AN: 438994 Hom.: 15628 AF XY: 0.254 AC XY: 58383 AN XY: 229590

African (AFR) AF: 0.277 AC: 3373 AN: 12184

American (AMR) AF: 0.353 AC: 6460 AN: 18308

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 4767 AN: 13242

East Asian (EAS) AF: 0.0793 AC: 2421 AN: 30526

South Asian (SAS) AF: 0.202 AC: 8798 AN: 43646

European-Finnish (FIN) AF: 0.219 AC: 6630 AN: 30270

Middle Eastern (MID) AF: 0.295 AC: 557 AN: 1890

European-Non Finnish (NFE) AF: 0.279 AC: 73471 AN: 263616

Other (OTH) AF: 0.267 AC: 6752 AN: 25312

GnomAD4 genome AF: 0.277 AC: 40208 AN: 145250 Hom.: 5609 Cov.: 22 AF XY: 0.270 AC XY: 19086 AN XY: 70588

African (AFR) AF: 0.282 AC: 10840 AN: 38470

American (AMR) AF: 0.328 AC: 4687 AN: 14286

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1271 AN: 3402

East Asian (EAS) AF: 0.0686 AC: 348 AN: 5076

South Asian (SAS) AF: 0.189 AC: 847 AN: 4480

European-Finnish (FIN) AF: 0.210 AC: 2098 AN: 9976

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.289 AC: 19190 AN: 66440

Other (OTH) AF: 0.280 AC: 547 AN: 1954

Alfa AF: 0.297 Hom.: 678

Bravo AF: 0.296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.1
DANN	Benign	0.62
PhyloP100		1.5
PromoterAI		0.024	Neutral

Splicing

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

Other links and lift over

dbSNP: rs4803219; hg19: chr19-39735919;