Variant rs181206 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000356897.1(IL27):c.356T>C(p.Leu119Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,612,884 control chromosomes in the GnomAD database, including 79,847 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.24 ( 5821 hom., cov: 32)

Exomes 𝑓: 0.31 ( 74026 hom. )

Consequence

IL27
ENST00000356897.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.24

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046949387).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL27	NM_145659.3 linkuse as main transcript	c.356T>C	p.Leu119Pro	missense_variant	4/5	ENST00000356897.1	NP_663634.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL27	ENST00000356897.1 linkuse as main transcript	c.356T>C	p.Leu119Pro	missense_variant	4/5	1	NM_145659.3	ENSP00000349365	P1
IL27	ENST00000568075.1 linkuse as main transcript	c.-38T>C		5_prime_UTR_variant	4/4	5		ENSP00000455990

Frequencies

GnomAD3 genomes

AF:

0.241

AC:

36558

AN:

151988

Hom.:

5813

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0592

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.255

Gnomad EAS

AF:

0.0778

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.422

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.329

Gnomad OTH

AF:

0.236

GnomAD3 exomes

AF:

0.283

AC:

70390

AN:

248574

Hom.:

11420

AF XY:

0.281

AC XY:

37777

AN XY:

134444

show subpopulations

Gnomad AFR exome

AF:

0.0547

Gnomad AMR exome

AF:

0.356

Gnomad ASJ exome

AF:

0.253

Gnomad EAS exome

AF:

0.0714

Gnomad SAS exome

AF:

0.194

Gnomad FIN exome

AF:

0.418

Gnomad NFE exome

AF:

0.329

Gnomad OTH exome

AF:

0.294

GnomAD4 exome

AF:

0.310

AC:

452619

AN:

1460778

Hom.:

74026

Cov.:

AF XY:

0.307

AC XY:

223375

AN XY:

726694

show subpopulations

Gnomad4 AFR exome

AF:

0.0470

Gnomad4 AMR exome

AF:

0.359

Gnomad4 ASJ exome

AF:

0.251

Gnomad4 EAS exome

AF:

0.0993

Gnomad4 SAS exome

AF:

0.196

Gnomad4 FIN exome

AF:

0.418

Gnomad4 NFE exome

AF:

0.331

Gnomad4 OTH exome

AF:

0.277

GnomAD4 genome

AF:

0.240

AC:

36575

AN:

152106

Hom.:

5821

Cov.:

AF XY:

0.242

AC XY:

17986

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0590

Gnomad4 AMR

AF:

0.291

Gnomad4 ASJ

AF:

0.255

Gnomad4 EAS

AF:

0.0780

Gnomad4 SAS

AF:

0.185

Gnomad4 FIN

AF:

0.422

Gnomad4 NFE

AF:

0.329

Gnomad4 OTH

AF:

0.234

Alfa

AF:

0.297

Hom.:

9864

Bravo

AF:

0.225

TwinsUK

AF:

0.337

AC:

1248

ALSPAC

AF:

0.330

AC:

1272

ESP6500AA

AF:

0.0728

AC:

320

ESP6500EA

AF:

0.320

AC:

2753

ExAC

AF:

0.276

AC:

33503

Asia WGS

AF:

0.161

AC:

559

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.53

MetaRNN

Benign

0.0047

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.046

Sift

Uncertain

0.0020

Sift4G

Benign

0.10

Polyphen

0.99

Vest4

0.15

MPC

1.4

ClinPred

0.028

GERP RS

3.0

Varity_R

0.63

gMVP

0.90

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over