rs4803217

Positions:

• chr19-39243580-C-A
• chr19-39243580-C-T

Variant summary

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

The NM_172139.4(IFNL3):​c.*52G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,529,100 control chromosomes in the GnomAD database, including 78,205 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 0.38 (12876 hom., cov: 32)
  • Exomes 𝑓: 0.30 (65329 hom.)
• Consequence: IFNL3 NM_172139.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.817

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNL3	NM_172139.4	c.*52G>T		3_prime_UTR_variant	5/5	ENST00000413851.3	NP_742151.2
IFNL3	NM_001346937.2	c.*52G>T		3_prime_UTR_variant	6/6		NP_001333866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNL3	ENST00000413851.3	c.*52G>T		3_prime_UTR_variant	5/5	1	NM_172139.4	ENSP00000409000.2
IFNL3	ENST00000613087.5	c.*52G>T		3_prime_UTR_variant	6/6	1		ENSP00000481633.1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58225 AN: 151902 Hom.: 12844 Cov.: 32

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.0711

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.363

GnomAD4 exome AF: 0.299 AC: 411119 AN: 1377080 Hom.: 65329 Cov.: 29 AF XY: 0.296 AC XY: 201103 AN XY: 679968

Gnomad4 AFR exome AF: 0.602

Gnomad4 AMR exome AF: 0.399

Gnomad4 ASJ exome AF: 0.377

Gnomad4 EAS exome AF: 0.0823

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.249

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.384 AC: 58305 AN: 152020 Hom.: 12876 Cov.: 32 AF XY: 0.374 AC XY: 27803 AN XY: 74292

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.0715

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.359

Alfa AF: 0.298 Hom.: 1041

Bravo AF: 0.404

Asia WGS AF: 0.190 AC: 666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.5
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4803217; hg19: chr19-39734220; COSMIC: COSV69830048; COSMIC: COSV69830048;