Variant 19-39244094-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_172139.4(IFNL3):c.322A>G(p.Thr108Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00754 in 1,613,654 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0065 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 68 hom. )

Consequence

IFNL3
NM_172139.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.48

Variant links:

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]

IFNL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004872024).

BP6

Variant 19-39244094-T-C is Benign according to our data. Variant chr19-39244094-T-C is described in ClinVar as [Benign]. Clinvar id is 788661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 992 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNL3	NM_172139.4 linkuse as main transcript	c.322A>G	p.Thr108Ala	missense_variant	3/5	ENST00000413851.3	NP_742151.2
IFNL3	NM_001346937.2 linkuse as main transcript	c.334A>G	p.Thr112Ala	missense_variant	4/6		NP_001333866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNL3	ENST00000413851.3 linkuse as main transcript	c.322A>G	p.Thr108Ala	missense_variant	3/5	1	NM_172139.4	ENSP00000409000	A2
IFNL3	ENST00000613087.5 linkuse as main transcript	c.334A>G	p.Thr112Ala	missense_variant	4/6	1		ENSP00000481633	P4

Frequencies

GnomAD3 genomes

AF:

0.00653

AC:

992

AN:

151852

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00721

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00328

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0100

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00755

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00614

AC:

1543

AN:

251362

Hom.:

AF XY:

0.00644

AC XY:

875

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.00807

Gnomad AMR exome

AF:

0.00266

Gnomad ASJ exome

AF:

0.0160

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00970

Gnomad FIN exome

AF:

0.000508

Gnomad NFE exome

AF:

0.00710

Gnomad OTH exome

AF:

0.00701

GnomAD4 exome

AF:

0.00764

AC:

11169

AN:

1461686

Hom.:

Cov.:

AF XY:

0.00764

AC XY:

5556

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.00748

Gnomad4 AMR exome

AF:

0.00282

Gnomad4 ASJ exome

AF:

0.0169

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00960

Gnomad4 FIN exome

AF:

0.000505

Gnomad4 NFE exome

AF:

0.00797

Gnomad4 OTH exome

AF:

0.00899

GnomAD4 genome

AF:

0.00653

AC:

992

AN:

151968

Hom.:

Cov.:

AF XY:

0.00611

AC XY:

454

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.00722

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.0170

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00981

Gnomad4 FIN

AF:

0.000284

Gnomad4 NFE

AF:

0.00755

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00770

Hom.:

Bravo

AF:

0.00665

ESP6500AA

AF:

0.00840

AC:

ESP6500EA

AF:

0.00779

AC:

ExAC

AF:

0.00624

AC:

758

EpiCase

AF:

0.00714

EpiControl

AF:

0.00777

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.0060

DANN

Benign

0.26

DEOGEN2

Benign

0.0021

.;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0012

LIST_S2

Benign

0.066

T;T

MetaRNN

Benign

0.0049

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.81

.;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

0.070

.;N

REVEL

Benign

0.027

Sift

Benign

0.60

.;T

Sift4G

Benign

0.56

T;T

Polyphen

0.0

.;B

Vest4

0.095

MVP

0.055

MPC

0.19

ClinPred

0.00068

GERP RS

-5.9

Varity_R

0.061

gMVP

0.063

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over