Variant chr19-39243850-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_172139.4(IFNL3):c.466C>T(p.His156Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00485 in 1,606,278 control chromosomes in the GnomAD database, including 284 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 75 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 209 hom. )

Consequence

IFNL3
NM_172139.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.89

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003402114).

BP6

Variant 19-39243850-G-A is Benign according to our data. Variant chr19-39243850-G-A is described in ClinVar as [Benign]. Clinvar id is 771518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNL3	NM_172139.4 linkuse as main transcript	c.466C>T	p.His156Tyr	missense_variant	4/5	ENST00000413851.3	NP_742151.2
IFNL3	NM_001346937.2 linkuse as main transcript	c.478C>T	p.His160Tyr	missense_variant	5/6		NP_001333866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNL3	ENST00000413851.3 linkuse as main transcript	c.466C>T	p.His156Tyr	missense_variant	4/5	1	NM_172139.4	ENSP00000409000	A2
IFNL3	ENST00000613087.5 linkuse as main transcript	c.478C>T	p.His160Tyr	missense_variant	5/6	1		ENSP00000481633	P4

Frequencies

GnomAD3 genomes

AF:

0.0117

AC:

1784

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0816

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00289

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00320

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00375

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.0100

AC:

2467

AN:

246580

Hom.:

136

AF XY:

0.00774

AC XY:

1037

AN XY:

134000

show subpopulations

Gnomad AFR exome

AF:

0.00284

Gnomad AMR exome

AF:

0.0670

Gnomad ASJ exome

AF:

0.000697

Gnomad EAS exome

AF:

0.00152

Gnomad SAS exome

AF:

0.000622

Gnomad FIN exome

AF:

0.00153

Gnomad NFE exome

AF:

0.00151

Gnomad OTH exome

AF:

0.00932

GnomAD4 exome

AF:

0.00412

AC:

5994

AN:

1454082

Hom.:

209

Cov.:

AF XY:

0.00377

AC XY:

2730

AN XY:

723794

show subpopulations

Gnomad4 AFR exome

AF:

0.00252

Gnomad4 AMR exome

AF:

0.0743

Gnomad4 ASJ exome

AF:

0.000727

Gnomad4 EAS exome

AF:

0.000983

Gnomad4 SAS exome

AF:

0.00114

Gnomad4 FIN exome

AF:

0.00250

Gnomad4 NFE exome

AF:

0.00195

Gnomad4 OTH exome

AF:

0.00605

GnomAD4 genome

AF:

0.0118

AC:

1794

AN:

152196

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

974

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00485

Gnomad4 AMR

AF:

0.0822

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00290

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00320

Gnomad4 NFE

AF:

0.00375

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00482

Hom.:

Bravo

AF:

0.0177

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00311

AC:

ExAC

AF:

0.00740

AC:

898

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.087

.;T

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.47

T;T

MetaRNN

Benign

0.0034

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.3

.;M

MutationTaster

Benign

0.50

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-4.6

.;D

REVEL

Benign

0.21

Sift

Benign

0.076

.;T

Sift4G

Benign

0.066

T;T

Polyphen

0.99

.;D

Vest4

0.32

MPC

0.71

ClinPred

0.028

GERP RS

4.0

Varity_R

0.19

gMVP

0.15

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