rs26528

Positions:

• chr16-28506388-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	Protein	UniProt
IL27	NM_145659.3	c.31+393A>G		intron_variant		ENST00000356897.1	NP_663634.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL27	ENST00000356897.1	c.31+393A>G		intron_variant		1	NM_145659.3	ENSP00000349365.1
IL27	ENST00000568075.1	c.-362-2338A>G		intron_variant		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

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.480

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.396

Alfa AF: 0.441 Hom.: 15842

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs26528; hg19: chr16-28517709;