rs181206

Variant names:

• chr16-28502082-A-G
• rs181206
• NM_145659.3:c.356T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145659.3(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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L119Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.24 (5821 hom., cov: 32)
  • Exomes 𝑓: 0.31 (74026 hom.)
• Consequence: IL27 NM_145659.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 99 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145659.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL27	NM_145659.3	MANE Select	c.356T>C	p.Leu119Pro	missense	Exon 4 of 5	NP_663634.2	Q8NEV9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL27	ENST00000356897.1	TSL:1 MANE Select	c.356T>C	p.Leu119Pro	missense	Exon 4 of 5	ENSP00000349365.1	Q8NEV9
	IL27	ENST00000568075.1	TSL:5	c.-38T>C		5_prime_UTR	Exon 4 of 4	ENSP00000455990.1	H3BQY2

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36558 AN: 151988 Hom.: 5813 Cov.: 32

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

GnomAD2 exomes AF: 0.283 AC: 70390 AN: 248574 AF XY: 0.281

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 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.: 36 AF XY: 0.307 AC XY: 223375 AN XY: 726694

African (AFR) AF: 0.0470 AC: 1574 AN: 33468

American (AMR) AF: 0.359 AC: 15996 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 6563 AN: 26116

East Asian (EAS) AF: 0.0993 AC: 3938 AN: 39652

South Asian (SAS) AF: 0.196 AC: 16933 AN: 86230

European-Finnish (FIN) AF: 0.418 AC: 22207 AN: 53152

Middle Eastern (MID) AF: 0.197 AC: 1133 AN: 5742

European-Non Finnish (NFE) AF: 0.331 AC: 367531 AN: 1111488

Other (OTH) AF: 0.277 AC: 16744 AN: 60342

GnomAD4 genome AF: 0.240 AC: 36575 AN: 152106 Hom.: 5821 Cov.: 32 AF XY: 0.242 AC XY: 17986 AN XY: 74348

African (AFR) AF: 0.0590 AC: 2452 AN: 41528

American (AMR) AF: 0.291 AC: 4440 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 884 AN: 3470

East Asian (EAS) AF: 0.0780 AC: 404 AN: 5180

South Asian (SAS) AF: 0.185 AC: 892 AN: 4826

European-Finnish (FIN) AF: 0.422 AC: 4454 AN: 10558

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22357 AN: 67958

Other (OTH) AF: 0.234 AC: 493 AN: 2108

Alfa AF: 0.289 Hom.: 24587

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.2
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.046
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.10	T
Polyphen		0.99	D
Vest4		0.15
MPC		1.4
ClinPred		0.028	T
GERP RS		3.0
Varity_R		0.63
gMVP		0.90
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs181206; hg19: chr16-28513403; COSMIC: COSV60489019; COSMIC: COSV60489019;