16-28506388-T-C

Variant names:

• chr16-28506388-T-C
• rs26528
• NM_145659.3:c.31+393A>G

Variant summary

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

The NM_145659.3(IL27):​c.31+393A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,030 control chromosomes in the GnomAD database, including 14,736 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.

• Frequency: Genomes: 𝑓 0.43 (14736 hom., cov: 32)
• Consequence: IL27 NM_145659.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.883
• Publications: 77 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 (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL27	NM_145659.3	c.31+393A>G		intron_variant	Intron 1 of 4	ENST00000356897.1	NP_663634.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL27	ENST00000356897.1	c.31+393A>G		intron_variant	Intron 1 of 4	1	NM_145659.3	ENSP00000349365.1
IL27	ENST00000568075.1	c.-362-2338A>G		intron_variant	Intron 1 of 3	5		ENSP00000455990.1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65460 AN: 151912 Hom.: 14711 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.391

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.431 AC: 65534 AN: 152030 Hom.: 14736 Cov.: 32 AF XY: 0.432 AC XY: 32060 AN XY: 74290

African (AFR) AF: 0.366 AC: 15175 AN: 41452

American (AMR) AF: 0.480 AC: 7319 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1205 AN: 3470

East Asian (EAS) AF: 0.384 AC: 1986 AN: 5174

South Asian (SAS) AF: 0.298 AC: 1437 AN: 4824

European-Finnish (FIN) AF: 0.545 AC: 5753 AN: 10562

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31402 AN: 67978

Other (OTH) AF: 0.396 AC: 836 AN: 2112

Alfa AF: 0.443 Hom.: 41548

Bravo AF: 0.430

Asia WGS AF: 0.404 AC: 1401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.23
DANN	Benign	0.21
PhyloP100		-0.88
PromoterAI		-0.0020	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs26528; hg19: chr16-28517709;