Variant 19-39248513-CTT-CT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000634967.1(IFNL4):c.66del(p.Gly23AlafsTer110) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 13877 hom., cov: 0)

Exomes 𝑓: 0.31 ( 53187 hom. )

Consequence

IFNL4
ENST00000634967.1 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.629 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.343del		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	Appris
IFNL4	ENST00000634967.1 linkuse as main transcript	c.66del	p.Gly23AlafsTer110	frameshift_variant	1/4	1	ENSP00000489559	P5
IFNL4	ENST00000606380.2 linkuse as main transcript	c.66del	p.Gly23AlafsTer158	frameshift_variant	1/5	1	ENSP00000476098	A2
IFNL4	ENST00000634680.1 linkuse as main transcript	c.66del	p.Gly23AlafsTer86	frameshift_variant	1/3	1	ENSP00000489240	A2

Frequencies

GnomAD3 genomes

AF:

0.396

AC:

60151

AN:

151764

Hom.:

13844

Cov.:

show subpopulations

Gnomad AFR

AF:

0.635

Gnomad AMI

AF:

0.367

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.393

Gnomad EAS

AF:

0.0683

Gnomad SAS

AF:

0.234

Gnomad FIN

AF:

0.240

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.317

Gnomad OTH

AF:

0.376

GnomAD3 exomes

AF:

0.222

AC:

AN:

Hom.:

AF XY:

0.125

AC XY:

AN XY:

show subpopulations

Gnomad AFR exome

AF:

0.500

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.250

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.306

AC:

330720

AN:

1079170

Hom.:

53187

Cov.:

AF XY:

0.306

AC XY:

156109

AN XY:

509462

show subpopulations

Gnomad4 AFR exome

AF:

0.649

Gnomad4 AMR exome

AF:

0.403

Gnomad4 ASJ exome

AF:

0.388

Gnomad4 EAS exome

AF:

0.0867

Gnomad4 SAS exome

AF:

0.242

Gnomad4 FIN exome

AF:

0.260

Gnomad4 NFE exome

AF:

0.304

Gnomad4 OTH exome

AF:

0.306

GnomAD4 genome

AF:

0.397

AC:

60233

AN:

151882

Hom.:

13877

Cov.:

AF XY:

0.387

AC XY:

28714

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.636

Gnomad4 AMR

AF:

0.379

Gnomad4 ASJ

AF:

0.393

Gnomad4 EAS

AF:

0.0686

Gnomad4 SAS

AF:

0.234

Gnomad4 FIN

AF:

0.240

Gnomad4 NFE

AF:

0.317

Gnomad4 OTH

AF:

0.372

Alfa

AF:

0.377

Hom.:

1434

Bravo

AF:

0.420

Asia WGS

AF:

0.199

AC:

696

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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