Variant 19-39247226-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000634967.1(IFNL4):c.304G>C(p.Ala102Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,230,816 control chromosomes in the GnomAD database, including 24,612 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 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 0.20 ( 3368 hom., cov: 32)

Exomes 𝑓: 0.20 ( 21244 hom. )

Consequence

IFNL4
ENST00000634967.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.21

Variant links:

Genes affected

IFNL4 (HGNC:44480): (interferon lambda 4 (gene/pseudogene)) This gene is a polymorphic pseudogene which, in some humans, encodes the interferon (IFN) lambda 4 protein. Humans are polymorphic for the dinucleotide TT/deltaG allele. Compared to the ancestral state in non-human primates, the TT allele produces a frameshift in the coding region of this gene which is predicted to induce nonsense-mediated mRNA decay. This allele, and an allele in the first intron of this gene, have experienced a rapid increase in frequency and show indications of positive selection. The ancestral states of these alleles are associated with an impaired ability to clear hepatitis C virus. This gene, like other type III interferons (IFNs), interacts with the IFN lambda receptor complex (IFNLR) whose signaling is generally restricted to epithelial cells. This gene resides in a cluster of four type III IFN genes and at least two pseudogenes on chromosome 19q13.2. In general, interferons are produced in response to viral infection and block viral replication and propagation to uninfected cells by activating the JAK-STAT pathway and up-regulating antiviral genes. Multiple alternatively spliced transcripts have been described for this gene but their biological validity and protein coding status is still being ascertained. [provided by RefSeq, May 2017]

IFNL4 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 (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNL4	NR_074079.1 linkuse as main transcript	n.725G>C		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	Appris
IFNL4	ENST00000634967.1 linkuse as main transcript	c.304G>C	p.Ala102Pro	missense_variant	4/4	1	ENSP00000489559	P5
IFNL4	ENST00000634680.1 linkuse as main transcript	c.232G>C	p.Ala78Pro	missense_variant	3/3	1	ENSP00000489240	A2
IFNL4	ENST00000606380.2 linkuse as main transcript	c.*76G>C		3_prime_UTR_variant	5/5	1	ENSP00000476098	A2

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

31148

AN:

152032

Hom.:

3365

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.279

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.0636

Gnomad SAS

AF:

0.161

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.212

GnomAD3 exomes

AF:

0.250

AC:

AN:

Hom.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

Gnomad FIN exome

AF:

0.250

Gnomad NFE exome

AF:

0.233

Gnomad OTH exome

AF:

0.500

GnomAD4 exome

AF:

0.196

AC:

211639

AN:

1078666

Hom.:

21244

Cov.:

AF XY:

0.197

AC XY:

100310

AN XY:

509256

show subpopulations

Gnomad4 AFR exome

AF:

0.215

Gnomad4 AMR exome

AF:

0.310

Gnomad4 ASJ exome

AF:

0.230

Gnomad4 EAS exome

AF:

0.0821

Gnomad4 SAS exome

AF:

0.166

Gnomad4 FIN exome

AF:

0.146

Gnomad4 NFE exome

AF:

0.200

Gnomad4 OTH exome

AF:

0.189

GnomAD4 genome

AF:

0.205

AC:

31181

AN:

152150

Hom.:

3368

Cov.:

AF XY:

0.200

AC XY:

14887

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.221

Gnomad4 AMR

AF:

0.278

Gnomad4 ASJ

AF:

0.234

Gnomad4 EAS

AF:

0.0639

Gnomad4 SAS

AF:

0.161

Gnomad4 FIN

AF:

0.137

Gnomad4 NFE

AF:

0.201

Gnomad4 OTH

AF:

0.210

Alfa

AF:

0.114

Hom.:

173

Bravo

AF:

0.218

Asia WGS

AF:

0.114

AC:

398

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.1

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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