rs628973

Positions:

• chr19-39244626-T-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000413851.3(IFNL3):​c.181-132A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00492 in 1,366,834 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0066 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0047 (28 hom.)
• Consequence: IFNL3 ENST00000413851.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BS2: High AC in GnomAd4 at 1008 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNL3	NM_172139.4	c.181-132A>T		intron_variant		ENST00000413851.3	NP_742151.2
IFNL3	NM_001346937.2	c.193-132A>T		intron_variant			NP_001333866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNL3	ENST00000413851.3	c.181-132A>T		intron_variant		1	NM_172139.4	ENSP00000409000	A2
IFNL3	ENST00000613087.5	c.193-132A>T		intron_variant		1		ENSP00000481633	P4

Frequencies

GnomAD3 genomes AF: 0.00665 AC: 1010 AN: 151766 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.00167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0125

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.00498

Gnomad FIN AF: 0.000945

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00874

Gnomad OTH AF: 0.0115

GnomAD4 exome AF: 0.00470 AC: 5711 AN: 1214950 Hom.: 28 Cov.: 18 AF XY: 0.00490 AC XY: 2926 AN XY: 596886

Gnomad4 AFR exome AF: 0.00145

Gnomad4 AMR exome AF: 0.00796

Gnomad4 ASJ exome AF: 0.0195

Gnomad4 EAS exome AF: 0.000429

Gnomad4 SAS exome AF: 0.00547

Gnomad4 FIN exome AF: 0.00166

Gnomad4 NFE exome AF: 0.00454

Gnomad4 OTH exome AF: 0.00643

GnomAD4 genome AF: 0.00664 AC: 1008 AN: 151884 Hom.: 2 Cov.: 31 AF XY: 0.00690 AC XY: 512 AN XY: 74238

Gnomad4 AFR AF: 0.00167

Gnomad4 AMR AF: 0.0124

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.000969

Gnomad4 SAS AF: 0.00499

Gnomad4 FIN AF: 0.000945

Gnomad4 NFE AF: 0.00873

Gnomad4 OTH AF: 0.0119

Alfa AF: 0.00772 Hom.: 0

Bravo AF: 0.00692

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs628973; hg19: chr19-39735266;