dbSNP rs628973: 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:

Genome browser will be placed here

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172139.4. 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
	IFNL3	NM_172139.4	MANE Select	c.181-132A>T		intron	N/A	NP_742151.2
	IFNL3	NM_001346937.2		c.193-132A>T		intron	N/A	NP_001333866.1	A0A0C4DGW8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNL3	ENST00000413851.3	TSL:1 MANE Select	c.181-132A>T		intron	N/A	ENSP00000409000.2	Q8IZI9
	IFNL3	ENST00000613087.5	TSL:1	c.193-132A>T		intron	N/A	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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over