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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNL3	NM_172139.4 link	c.-37G>C		5_prime_UTR_variant	Exon 1 of 5	ENST00000413851.3	NP_742151.2
IFNL3	NM_001346937.2 link	c.11-35G>C		intron_variant	Intron 1 of 5		NP_001333866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNL3	ENST00000413851.3 link	c.-37G>C		5_prime_UTR_variant	Exon 1 of 5	1	NM_172139.4	ENSP00000409000.2
IFNL3	ENST00000613087.5 link	c.11-35G>C		intron_variant	Intron 1 of 5	1		ENSP00000481633.1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over