rs11322783

Variant names:

• chr19-39248514-TT-G
• rs11322783
• ENST00000634967.1:c.65_66delAAinsC

Your query was ambiguous. Multiple possible variants found:

• chr19-39248513-CTT-CG
• chr19-39248513-CTT-CT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000634967.1(IFNL4):​c.65_66delAAinsC​(p.Glu22AlafsTer111) variant causes a frameshift, missense 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: not found (cov: 0)
• Consequence: IFNL4 ENST00000634967.1 frameshift, missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 28 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000634967.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNL4	NR_074079.1		n.342_343delAAinsC		non_coding_transcript_exon	Exon 1 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNL4	ENST00000634967.1	TSL:1	c.65_66delAAinsC	p.Glu22AlafsTer111	frameshift missense	Exon 1 of 4	ENSP00000489559.1
	IFNL4	ENST00000606380.2	TSL:1	c.65_66delAAinsC	p.Glu22AlafsTer159	frameshift missense	Exon 1 of 5	ENSP00000476098.2	K9M1I6
	IFNL4	ENST00000634680.1	TSL:1	c.65_66delAAinsC	p.Glu22AlafsTer87	frameshift missense	Exon 1 of 3	ENSP00000489240.1

Frequencies

GnomAD3 genomes Cov.: 0

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11322783; hg19: chr19-39739154;