16-28503907-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_145659.3(IL27):c.175T>G(p.Ser59Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0524 in 1,614,126 control chromosomes in the GnomAD database, including 2,547 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 256 hom., cov: 33)

Exomes 𝑓: 0.052 ( 2291 hom. )

Consequence

IL27
NM_145659.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.56

Publications

75 publications found

Variant links:

Genes affected

IL27 (HGNC:19157): (interleukin 27) The protein encoded by this gene is one of the subunits of a heterodimeric cytokine complex. This protein is related to interleukin 12A (IL12A). It interacts with Epstein-Barr virus induced gene 3 (EBI3), a protein similar to interleukin 12B (IL12B), and forms a complex that has been shown to drive rapid expansion of naive but not memory CD4(+) T cells. The complex is also found to synergize strongly with interleukin 12 to trigger interferon gamma (IFNG) production of naive CD4(+) T cells. The biological effects of this cytokine are mediated by the class I cytokine receptor (WSX1/TCRR). [provided by RefSeq, Jul 2008]

IL27 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00139606).

BP6

Variant 16-28503907-A-C is Benign according to our data. Variant chr16-28503907-A-C is described in ClinVar as Benign. ClinVar VariationId is 1273271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL27	NM_145659.3 link	c.175T>G	p.Ser59Ala	missense_variant	Exon 2 of 5	ENST00000356897.1	NP_663634.2	Q8NEV9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL27	ENST00000356897.1 link	c.175T>G	p.Ser59Ala	missense_variant	Exon 2 of 5	1	NM_145659.3	ENSP00000349365.1		Q8NEV9
IL27	ENST00000568075.1 link	c.-219T>G		5_prime_UTR_variant	Exon 2 of 4	5		ENSP00000455990.1		H3BQY2

Frequencies

GnomAD3 genomes

AF:

0.0570

AC:

8678

AN:

152184

Hom.:

256

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0695

Gnomad AMI

AF:

0.152

Gnomad AMR

AF:

0.0559

Gnomad ASJ

AF:

0.0357

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.0726

Gnomad FIN

AF:

0.0516

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0457

Gnomad OTH

AF:

0.0498

GnomAD2 exomes

AF:

0.0640

AC:

16047

AN:

250916

AF XY:

0.0609

show subpopulations

Gnomad AFR exome

AF:

0.0706

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.0355

Gnomad EAS exome

AF:

0.116

Gnomad FIN exome

AF:

0.0491

Gnomad NFE exome

AF:

0.0429

Gnomad OTH exome

AF:

0.0490

GnomAD4 exome

AF:

0.0519

AC:

75931

AN:

1461824

Hom.:

2291

Cov.:

AF XY:

0.0517

AC XY:

37578

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.0742

AC:

2485

AN:

33478

American (AMR)

AF:

0.107

AC:

4796

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0339

AC:

886

AN:

26126

East Asian (EAS)

AF:

0.111

AC:

4395

AN:

39694

South Asian (SAS)

AF:

0.0672

AC:

5798

AN:

86258

European-Finnish (FIN)

AF:

0.0477

AC:

2548

AN:

53400

Middle Eastern (MID)

AF:

0.0406

AC:

234

AN:

5768

European-Non Finnish (NFE)

AF:

0.0462

AC:

51359

AN:

1111986

Other (OTH)

AF:

0.0568

AC:

3430

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

4046

8092

12139

16185

20231

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2090

4180

6270

8360

10450

<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:

0.0571

AC:

8693

AN:

152302

Hom.:

256

Cov.:

AF XY:

0.0577

AC XY:

4296

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0694

AC:

2885

AN:

41560

American (AMR)

AF:

0.0559

AC:

855

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0357

AC:

124

AN:

3472

East Asian (EAS)

AF:

0.107

AC:

557

AN:

5182

South Asian (SAS)

AF:

0.0731

AC:

353

AN:

4832

European-Finnish (FIN)

AF:

0.0516

AC:

548

AN:

10622

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0458

AC:

3113

AN:

68024

Other (OTH)

AF:

0.0526

AC:

111

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

428

856

1284

1712

2140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<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:

0.0486

Hom.:

589

Bravo

AF:

0.0609

TwinsUK

AF:

0.0507

AC:

188

ALSPAC

AF:

0.0457

AC:

176

ESP6500AA

AF:

0.0710

AC:

312

ESP6500EA

AF:

0.0485

AC:

417

ExAC

AF:

0.0615

AC:

7470

Asia WGS

AF:

0.0890

AC:

307

AN:

3478

EpiCase

AF:

0.0473

EpiControl

AF:

0.0464

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 15, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 25075448, 24352695) -

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

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.20

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

1.6

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.1

REVEL

Benign

0.078

Sift

Benign

0.12

Sift4G

Benign

0.087

Polyphen

0.015

Vest4

0.043

MPC

0.32

ClinPred

0.0027

GERP RS

0.53

Varity_R

0.074

gMVP

0.38

Mutation Taster

=100/0

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over