rs4803219

Positions:

• chr19-39245279-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The 19-39245279-C-T 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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
IFNL3	NM_001346937.2			upstream_gene_variant			NP_001333866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNL3	ENST00000613087.5			upstream_gene_variant		1		ENSP00000481633	P4

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

Gnomad4 AFR exome AF: 0.277

Gnomad4 AMR exome AF: 0.353

Gnomad4 ASJ exome AF: 0.360

Gnomad4 EAS exome AF: 0.0793

Gnomad4 SAS exome AF: 0.202

Gnomad4 FIN exome AF: 0.219

Gnomad4 NFE exome AF: 0.279

Gnomad4 OTH exome AF: 0.267

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

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.0686

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.280

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4803219; hg19: chr19-39735919;