chr19-39245004-C-G

Position:

• chr19-39245004-C-G

Variant summary

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

The NM_172139.4(IFNL3):​c.-37G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,609,610 control chromosomes in the GnomAD database, including 83,364 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 (12797 hom., cov: 30)
  • Exomes 𝑓: 0.30 (70567 hom.)
• Consequence: IFNL3 NM_172139.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNL3	NM_172139.4	c.-37G>C		5_prime_UTR_variant	1/5	ENST00000413851.3	NP_742151.2
IFNL3	NM_001346937.2	c.11-35G>C		intron_variant			NP_001333866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNL3	ENST00000413851.3	c.-37G>C		5_prime_UTR_variant	1/5	1	NM_172139.4	ENSP00000409000	A2
IFNL3	ENST00000613087.5	c.11-35G>C		intron_variant		1		ENSP00000481633	P4

Frequencies

GnomAD3 genomes AF: 0.383 AC: 57878 AN: 151080 Hom.: 12765 Cov.: 30

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.0706

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.366

GnomAD3 exomes AF: 0.313 AC: 77750 AN: 248662 Hom.: 14018 AF XY: 0.301 AC XY: 40529 AN XY: 134556

Gnomad AFR exome AF: 0.610

Gnomad AMR exome AF: 0.414

Gnomad ASJ exome AF: 0.370

Gnomad EAS exome AF: 0.0655

Gnomad SAS exome AF: 0.220

Gnomad FIN exome AF: 0.246

Gnomad NFE exome AF: 0.313

Gnomad OTH exome AF: 0.326

GnomAD4 exome AF: 0.302 AC: 440284 AN: 1458410 Hom.: 70567 Cov.: 38 AF XY: 0.299 AC XY: 216694 AN XY: 725418

Gnomad4 AFR exome AF: 0.610

Gnomad4 AMR exome AF: 0.414

Gnomad4 ASJ exome AF: 0.377

Gnomad4 EAS exome AF: 0.0804

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.303

Gnomad4 OTH exome AF: 0.301

GnomAD4 genome AF: 0.383 AC: 57958 AN: 151200 Hom.: 12797 Cov.: 30 AF XY: 0.374 AC XY: 27628 AN XY: 73898

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.0709

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.362

Alfa AF: 0.360 Hom.: 1884

Bravo AF: 0.405

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.6
DANN	Benign	0.41

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

Other links and lift over

dbSNP: rs28416813; hg19: chr19-39735644; COSMIC: COSV69829814; COSMIC: COSV69829814;