rs11881222

Variant names:

• chr19-39244283-A-G
• rs11881222
• NM_172139.4:c.259-126T>C

Variant summary

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

The NM_172139.4(IFNL3):​c.259-126T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 1,480,780 control chromosomes in the GnomAD database, including 59,929 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (★★★).

• Frequency:
  • Genomes: 𝑓 0.30 (6936 hom., cov: 29)
  • Exomes 𝑓: 0.28 (52993 hom.)
• Consequence: IFNL3 NM_172139.4 intron
• Clinical Significance: drug response reviewed by expert panel O:3
• Conservation: PhyloP100: -0.860
• Publications: 76 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172139.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNL3	NM_172139.4	MANE Select	c.259-126T>C		intron	N/A	NP_742151.2
	IFNL3	NM_001346937.2		c.271-126T>C		intron	N/A	NP_001333866.1	A0A0C4DGW8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNL3	ENST00000413851.3	TSL:1 MANE Select	c.259-126T>C		intron	N/A	ENSP00000409000.2	Q8IZI9
	IFNL3	ENST00000613087.5	TSL:1	c.271-126T>C		intron	N/A	ENSP00000481633.1	A0A0C4DGW8

Frequencies

GnomAD3 genomes AF: 0.297 AC: 44904 AN: 151146 Hom.: 6925 Cov.: 29

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.0710

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.279 AC: 370626 AN: 1329516 Hom.: 52993 Cov.: 23 AF XY: 0.277 AC XY: 181980 AN XY: 656916

African (AFR) AF: 0.324 AC: 9991 AN: 30834

American (AMR) AF: 0.386 AC: 13776 AN: 35734

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 8439 AN: 22292

East Asian (EAS) AF: 0.0797 AC: 2992 AN: 37552

South Asian (SAS) AF: 0.221 AC: 16461 AN: 74454

European-Finnish (FIN) AF: 0.233 AC: 11249 AN: 48356

Middle Eastern (MID) AF: 0.303 AC: 1640 AN: 5406

European-Non Finnish (NFE) AF: 0.285 AC: 290800 AN: 1019344

Other (OTH) AF: 0.275 AC: 15278 AN: 55544

GnomAD4 genome AF: 0.297 AC: 44959 AN: 151264 Hom.: 6936 Cov.: 29 AF XY: 0.291 AC XY: 21496 AN XY: 73894

African (AFR) AF: 0.328 AC: 13488 AN: 41176

American (AMR) AF: 0.344 AC: 5235 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1349 AN: 3466

East Asian (EAS) AF: 0.0713 AC: 363 AN: 5090

South Asian (SAS) AF: 0.214 AC: 1021 AN: 4762

European-Finnish (FIN) AF: 0.220 AC: 2312 AN: 10494

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20151 AN: 67754

Other (OTH) AF: 0.298 AC: 627 AN: 2104

Alfa AF: 0.303 Hom.: 5559

Bravo AF: 0.310

Asia WGS AF: 0.157 AC: 549 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: drug response

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	-	peginterferon alfa-2a response - Efficacy (1)
-	-	-	peginterferon alfa-2b response - Efficacy (1)
-	-	-	ribavirin response - Efficacy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.8
DANN	Benign	0.68
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11881222; hg19: chr19-39734923; COSMIC: COSV69829920; COSMIC: COSV69829920;