Genetic Variant IFNL3:c.181-132A>T (chr19-39244626-T-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_172139.4(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
NM_172139.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.35

Publications

1 publications found

Variant links:

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]

IFNL3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IFNL3	NM_172139.4 link	c.181-132A>T		intron_variant	Intron 1 of 4	ENST00000413851.3	NP_742151.2	Q8IZI9A0A7R8C2Z6
IFNL3	NM_001346937.2 link	c.193-132A>T		intron_variant	Intron 2 of 5		NP_001333866.1	Q8IZI9A0A0C4DGW8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNL3	ENST00000413851.3 link	c.181-132A>T		intron_variant	Intron 1 of 4	1	NM_172139.4	ENSP00000409000.2		Q8IZI9
IFNL3	ENST00000613087.5 link	c.193-132A>T		intron_variant	Intron 2 of 5	1		ENSP00000481633.1		A0A0C4DGW8

Frequencies

GnomAD3 genomes

AF:

0.00665

AC:

1010

AN:

151766

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00490

AC XY:

2926

AN XY:

596886

show subpopulations

African (AFR)

AF:

0.00145

AC:

AN:

27522

American (AMR)

AF:

0.00796

AC:

232

AN:

29134

Ashkenazi Jewish (ASJ)

AF:

0.0195

AC:

384

AN:

19706

East Asian (EAS)

AF:

0.000429

AC:

AN:

34976

South Asian (SAS)

AF:

0.00547

AC:

367

AN:

67040

European-Finnish (FIN)

AF:

0.00166

AC:

AN:

47554

Middle Eastern (MID)

AF:

0.00796

AC:

AN:

3516

European-Non Finnish (NFE)

AF:

0.00454

AC:

4238

AN:

934476

Other (OTH)

AF:

0.00643

AC:

328

AN:

51026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.406

Heterozygous variant carriers

246

493

739

986

1232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

106

212

318

424

530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00664

AC:

1008

AN:

151884

Hom.:

Cov.:

AF XY:

0.00690

AC XY:

512

AN XY:

74238

show subpopulations

African (AFR)

AF:

0.00167

AC:

AN:

41320

American (AMR)

AF:

0.0124

AC:

189

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.0248

AC:

AN:

3468

East Asian (EAS)

AF:

0.000969

AC:

AN:

5162

South Asian (SAS)

AF:

0.00499

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.000945

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00873

AC:

593

AN:

67960

Other (OTH)

AF:

0.0119

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

142

189

236

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00772

Hom.:

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

(source)

DANN

Benign

0.56

PhyloP100

-1.3

PromoterAI

0.014

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over