rs8103362

Variant names:

• chr19-39269551-A-G
• rs8103362
• NM_172138.2:c.334A>G

Variant summary

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

The NM_172138.2(IFNL2):​c.334A>G​(p.Thr112Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,613,862 control chromosomes in the GnomAD database, including 41,486 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (4832 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36654 hom.)
• Consequence: IFNL2 NM_172138.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.62
• Publications: 20 publications found

Genes affected

IFNL2 (HGNC:18364): (interferon lambda 2) This gene encodes a cytokine distantly related to type I interferons and the IL-10 family. This gene, interleukin 28B (IL28B), 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 (MetaRNN=0.0038847327).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNL2	NM_172138.2	c.334A>G	p.Thr112Ala	missense_variant	Exon 4 of 6	ENST00000331982.6	NP_742150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNL2	ENST00000331982.6	c.334A>G	p.Thr112Ala	missense_variant	Exon 4 of 6	1	NM_172138.2	ENSP00000333639.5

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37098 AN: 151890 Hom.: 4831 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.0355

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.238

GnomAD2 exomes AF: 0.230 AC: 57762 AN: 251286 AF XY: 0.231

Gnomad AFR exome AF: 0.319

Gnomad AMR exome AF: 0.284

Gnomad ASJ exome AF: 0.240

Gnomad EAS exome AF: 0.0369

Gnomad FIN exome AF: 0.212

Gnomad NFE exome AF: 0.211

Gnomad OTH exome AF: 0.228

GnomAD4 exome AF: 0.218 AC: 318211 AN: 1461854 Hom.: 36654 Cov.: 37 AF XY: 0.221 AC XY: 160608 AN XY: 727220

African (AFR) AF: 0.314 AC: 10521 AN: 33478

American (AMR) AF: 0.280 AC: 12527 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 6293 AN: 26132

East Asian (EAS) AF: 0.0290 AC: 1150 AN: 39700

South Asian (SAS) AF: 0.318 AC: 27444 AN: 86256

European-Finnish (FIN) AF: 0.213 AC: 11396 AN: 53418

Middle Eastern (MID) AF: 0.297 AC: 1713 AN: 5766

European-Non Finnish (NFE) AF: 0.210 AC: 233819 AN: 1111996

Other (OTH) AF: 0.221 AC: 13348 AN: 60394

GnomAD4 genome AF: 0.244 AC: 37124 AN: 152008 Hom.: 4832 Cov.: 32 AF XY: 0.245 AC XY: 18202 AN XY: 74312

African (AFR) AF: 0.315 AC: 13041 AN: 41432

American (AMR) AF: 0.255 AC: 3895 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 821 AN: 3470

East Asian (EAS) AF: 0.0358 AC: 185 AN: 5166

South Asian (SAS) AF: 0.315 AC: 1519 AN: 4828

European-Finnish (FIN) AF: 0.215 AC: 2268 AN: 10566

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14513 AN: 67962

Other (OTH) AF: 0.236 AC: 496 AN: 2106

Alfa AF: 0.226 Hom.: 2644

Bravo AF: 0.248

TwinsUK AF: 0.221 AC: 819

ALSPAC AF: 0.210 AC: 808

ESP6500AA AF: 0.328 AC: 1447

ESP6500EA AF: 0.206 AC: 1774

ExAC AF: 0.229 AC: 27818

Asia WGS AF: 0.171 AC: 597 AN: 3476

EpiCase AF: 0.217

EpiControl AF: 0.211

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.014
DANN	Benign	0.32
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.066	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.26	N
PhyloP100		-4.6
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.0060
Sift	Benign	0.61	T
Sift4G	Benign	0.52	T
Polyphen		0.0	B
Vest4		0.027
MPC		0.31
ClinPred		0.00089	T
GERP RS		-6.2
Varity_R		0.023
gMVP		0.067
Mutation Taster		=98/2	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: rs8103362; hg19: chr19-39760191; COSMIC: COSV59593185; COSMIC: COSV59593185;