16-28503907-A-C

Position:

• chr16-28503907-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.057 (256 hom., cov: 33)
  • Exomes 𝑓: 0.052 (2291 hom.)
• Consequence: IL27 NM_145659.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.56

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
IL27	NM_145659.3	c.175T>G	p.Ser59Ala	missense_variant	2/5	ENST00000356897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL27	ENST00000356897.1	c.175T>G	p.Ser59Ala	missense_variant	2/5	1	NM_145659.3	P1
IL27	ENST00000568075.1	c.-219T>G		5_prime_UTR_variant	2/4	5

Frequencies

GnomAD3 genomes AF: 0.0570 AC: 8678 AN: 152184 Hom.: 256 Cov.: 33

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

GnomAD3 exomes AF: 0.0640 AC: 16047 AN: 250916 Hom.: 676 AF XY: 0.0609 AC XY: 8272 AN XY: 135764

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 SAS exome AF: 0.0700

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.: 32 AF XY: 0.0517 AC XY: 37578 AN XY: 727222

Gnomad4 AFR exome AF: 0.0742

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.0339

Gnomad4 EAS exome AF: 0.111

Gnomad4 SAS exome AF: 0.0672

Gnomad4 FIN exome AF: 0.0477

Gnomad4 NFE exome AF: 0.0462

Gnomad4 OTH exome AF: 0.0568

GnomAD4 genome AF: 0.0571 AC: 8693 AN: 152302 Hom.: 256 Cov.: 33 AF XY: 0.0577 AC XY: 4296 AN XY: 74478

Gnomad4 AFR AF: 0.0694

Gnomad4 AMR AF: 0.0559

Gnomad4 ASJ AF: 0.0357

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.0731

Gnomad4 FIN AF: 0.0516

Gnomad4 NFE AF: 0.0458

Gnomad4 OTH AF: 0.0526

Alfa AF: 0.0452 Hom.: 212

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

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2020	This variant is associated with the following publications: (PMID: 25075448, 24352695) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.078
Sift	Benign	0.12	T
Sift4G	Benign	0.087	T
Polyphen		0.015	B
Vest4		0.043
MPC		0.32
ClinPred		0.0027	T
GERP RS		0.53
Varity_R		0.074
gMVP		0.38

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

Other links and lift over

dbSNP: rs17855750; hg19: chr16-28515228; COSMIC: COSV60493848; COSMIC: COSV60493848;