Variant chr19-39269551-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.24 ( 4832 hom., cov: 32)

Exomes 𝑓: 0.22 ( 36654 hom. )

Consequence

IFNL2
NM_172138.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.62

Variant links:

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]

IFNL2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
IFNL2	NM_172138.2 linkuse as main transcript	c.334A>G	p.Thr112Ala	missense_variant	4/6	ENST00000331982.6	NP_742150.1	Q8IZJ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNL2	ENST00000331982.6 linkuse as main transcript	c.334A>G	p.Thr112Ala	missense_variant	4/6	1	NM_172138.2	ENSP00000333639.5		Q8IZJ0

Frequencies

GnomAD3 genomes

AF:

0.244

AC:

37098

AN:

151890

Hom.:

4831

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.230

AC:

57762

AN:

251286

Hom.:

7303

AF XY:

0.231

AC XY:

31439

AN XY:

135846

show subpopulations

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 SAS exome

AF:

0.315

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.:

AF XY:

0.221

AC XY:

160608

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.314

Gnomad4 AMR exome

AF:

0.280

Gnomad4 ASJ exome

AF:

0.241

Gnomad4 EAS exome

AF:

0.0290

Gnomad4 SAS exome

AF:

0.318

Gnomad4 FIN exome

AF:

0.213

Gnomad4 NFE exome

AF:

0.210

Gnomad4 OTH exome

AF:

0.221

GnomAD4 genome

AF:

0.244

AC:

37124

AN:

152008

Hom.:

4832

Cov.:

AF XY:

0.245

AC XY:

18202

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.315

Gnomad4 AMR

AF:

0.255

Gnomad4 ASJ

AF:

0.237

Gnomad4 EAS

AF:

0.0358

Gnomad4 SAS

AF:

0.315

Gnomad4 FIN

AF:

0.215

Gnomad4 NFE

AF:

0.214

Gnomad4 OTH

AF:

0.236

Alfa

AF:

0.231

Hom.:

2037

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

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.014

DANN

Benign

0.32

DEOGEN2

Benign

0.0053

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.066

MetaRNN

Benign

0.0039

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.26

PrimateAI

Benign

0.32

PROVEAN

Benign

0.070

REVEL

Benign

0.0060

Sift

Benign

0.61

Sift4G

Benign

0.52

Polyphen

0.0

Vest4

0.027

MPC

0.31

ClinPred

0.00089

GERP RS

-6.2

Varity_R

0.023

gMVP

0.067

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over