Variant 19-39298008-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_172140.2(IFNL1):c.294G>A(p.Thr98Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,614,158 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 4 hom., cov: 31)

Exomes 𝑓: 0.010 ( 97 hom. )

Consequence

IFNL1
NM_172140.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -7.77

Variant links:

Genes affected

IFNL1 (HGNC:18363): (interferon lambda 1) This gene encodes a cytokine distantly related to type I interferons and the IL-10 family. This gene, interleukin 28A (IL28A), and interleukin 28B (IL28B) 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]

IFNL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 19-39298008-G-A is Benign according to our data. Variant chr19-39298008-G-A is described in ClinVar as [Benign]. Clinvar id is 707833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-7.77 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNL1	NM_172140.2 linkuse as main transcript	c.294G>A	p.Thr98Thr	synonymous_variant	3/5	ENST00000333625.3	NP_742152.1	Q8IU54A0A7R8C391

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNL1	ENST00000333625.3 linkuse as main transcript	c.294G>A	p.Thr98Thr	synonymous_variant	3/5	1	NM_172140.2	ENSP00000329991.1		Q8IU54

Frequencies

GnomAD3 genomes

AF:

0.00716

AC:

1090

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0113

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00689

AC:

1732

AN:

251328

Hom.:

AF XY:

0.00712

AC XY:

967

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00567

Gnomad ASJ exome

AF:

0.00198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00291

Gnomad FIN exome

AF:

0.00120

Gnomad NFE exome

AF:

0.0116

Gnomad OTH exome

AF:

0.00962

GnomAD4 exome

AF:

0.0104

AC:

15236

AN:

1461866

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

7524

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00176

Gnomad4 AMR exome

AF:

0.00588

Gnomad4 ASJ exome

AF:

0.00180

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00276

Gnomad4 FIN exome

AF:

0.00170

Gnomad4 NFE exome

AF:

0.0125

Gnomad4 OTH exome

AF:

0.0100

GnomAD4 genome

AF:

0.00715

AC:

1089

AN:

152292

Hom.:

Cov.:

AF XY:

0.00638

AC XY:

475

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00180

Gnomad4 AMR

AF:

0.0115

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.0113

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00501

Hom.:

Bravo

AF:

0.00718

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0122

EpiControl

AF:

0.0135

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	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.071

DANN

Benign

0.42

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