dbSNP rs28416813: IFNL3:c.-37G>C (chr19-39245004-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_172139.4(IFNL3):c.-37G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,609,610 control chromosomes in the GnomAD database, including 83,364 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 0.38 ( 12797 hom., cov: 30)

Exomes 𝑓: 0.30 ( 70567 hom. )

Consequence

IFNL3
NM_172139.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.440

Publications

45 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

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.-37G>C		5_prime_UTR	Exon 1 of 5	NP_742151.2
	IFNL3	NM_001346937.2		c.11-35G>C		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.-37G>C		5_prime_UTR	Exon 1 of 5	ENSP00000409000.2	Q8IZI9
	IFNL3	ENST00000613087.5	TSL:1	c.11-35G>C		intron	N/A	ENSP00000481633.1	A0A0C4DGW8

Frequencies

GnomAD3 genomes

AF:

0.383

AC:

57878

AN:

151080

Hom.:

12765

Cov.:

show subpopulations

Gnomad AFR

AF:

0.604

Gnomad AMI

AF:

0.369

Gnomad AMR

AF:

0.372

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.0706

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.236

Gnomad MID

AF:

0.338

Gnomad NFE

AF:

0.312

Gnomad OTH

AF:

0.366

GnomAD2 exomes

AF:

0.313

AC:

77750

AN:

248662

AF XY:

0.301

show subpopulations

Gnomad AFR exome

AF:

0.610

Gnomad AMR exome

AF:

0.414

Gnomad ASJ exome

AF:

0.370

Gnomad EAS exome

AF:

0.0655

Gnomad FIN exome

AF:

0.246

Gnomad NFE exome

AF:

0.313

Gnomad OTH exome

AF:

0.326

GnomAD4 exome

AF:

0.302

AC:

440284

AN:

1458410

Hom.:

70567

Cov.:

AF XY:

0.299

AC XY:

216694

AN XY:

725418

show subpopulations

African (AFR)

AF:

0.610

AC:

20012

AN:

32788

American (AMR)

AF:

0.414

AC:

18380

AN:

44440

Ashkenazi Jewish (ASJ)

AF:

0.377

AC:

9795

AN:

26002

East Asian (EAS)

AF:

0.0804

AC:

3189

AN:

39688

South Asian (SAS)

AF:

0.224

AC:

19244

AN:

86004

European-Finnish (FIN)

AF:

0.250

AC:

13359

AN:

53358

Middle Eastern (MID)

AF:

0.295

AC:

1686

AN:

5718

European-Non Finnish (NFE)

AF:

0.303

AC:

336503

AN:

1110226

Other (OTH)

AF:

0.301

AC:

18116

AN:

60186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.419

Heterozygous variant carriers

16735

33470

50206

66941

83676

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10998

21996

32994

43992

54990

<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:

0.383

AC:

57958

AN:

151200

Hom.:

12797

Cov.:

AF XY:

0.374

AC XY:

27628

AN XY:

73898

show subpopulations

African (AFR)

AF:

0.605

AC:

24666

AN:

40800

American (AMR)

AF:

0.371

AC:

5653

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.382

AC:

1325

AN:

3466

East Asian (EAS)

AF:

0.0709

AC:

367

AN:

5174

South Asian (SAS)

AF:

0.218

AC:

1047

AN:

4806

European-Finnish (FIN)

AF:

0.236

AC:

2502

AN:

10580

Middle Eastern (MID)

AF:

0.339

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.313

AC:

21206

AN:

67858

Other (OTH)

AF:

0.362

AC:

757

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

1506

3013

4519

6026

7532

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

514

1028

1542

2056

2570

<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:

0.360

Hom.:

1884

Bravo

AF:

0.405

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.6

(source)

DANN

Benign

0.41

PhyloP100

0.44

PromoterAI

-0.0038

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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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