Genetic Variant NM_172140.2:c.294G>A (chr19-39298008-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_172140.2(IFNL1):c.294G>A(p.Thr98Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,614,158 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 4 hom., cov: 31)

Exomes 𝑓: 0.010 ( 97 hom. )

Consequence

IFNL1
NM_172140.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -7.77

Publications

3 publications found

Variant links:

Genes affected

IFNL1 (HGNC:18363): (interferon lambda 1) This gene encodes a cytokine distantly related to type I interferons and the IL-10 family. This gene, interleukin 28A (IL28A), and interleukin 28B (IL28B) 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]

IFNL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 19-39298008-G-A is Benign according to our data. Variant chr19-39298008-G-A is described in CliVar as Benign. Clinvar id is 707833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-39298008-G-A is described in CliVar as Benign. Clinvar id is 707833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-7.77 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNL1	NM_172140.2 link	c.294G>A	p.Thr98Thr	synonymous_variant	Exon 3 of 5	ENST00000333625.3	NP_742152.1	Q8IU54A0A7R8C391

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNL1	ENST00000333625.3 link	c.294G>A	p.Thr98Thr	synonymous_variant	Exon 3 of 5	1	NM_172140.2	ENSP00000329991.1		Q8IU54

Frequencies

GnomAD3 genomes

AF:

0.00716

AC:

1090

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0113

Gnomad OTH

AF:

0.00860

GnomAD2 exomes

AF:

0.00689

AC:

1732

AN:

251328

AF XY:

0.00712

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00567

Gnomad ASJ exome

AF:

0.00198

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00120

Gnomad NFE exome

AF:

0.0116

Gnomad OTH exome

AF:

0.00962

GnomAD4 exome

AF:

0.0104

AC:

15236

AN:

1461866

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

7524

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00176

AC:

AN:

33480

American (AMR)

AF:

0.00588

AC:

263

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00180

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00276

AC:

238

AN:

86258

European-Finnish (FIN)

AF:

0.00170

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00884

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0125

AC:

13882

AN:

1111996

Other (OTH)

AF:

0.0100

AC:

605

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

878

1755

2633

3510

4388

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

528

1056

1584

2112

2640

<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:

0.00715

AC:

1089

AN:

152292

Hom.:

Cov.:

AF XY:

0.00638

AC XY:

475

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00180

AC:

AN:

41568

American (AMR)

AF:

0.0115

AC:

176

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00403

AC:

AN:

3470

East Asian (EAS)

AF:

0.000194

AC:

AN:

5156

South Asian (SAS)

AF:

0.00311

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00179

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0113

AC:

768

AN:

68020

Other (OTH)

AF:

0.00851

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

110

165

220

275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00501

Hom.:

Bravo

AF:

0.00718

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0122

EpiControl

AF:

0.0135

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.071

(source)

DANN

Benign

0.42

PhyloP100

-7.8

Mutation Taster

=100/0

polymorphism

(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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over