rs1179251

Variant names:

• chr12-68251271-C-G
• rs1179251
• NM_020525.5:c.462+242G>C

Variant summary

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

The NM_020525.5(IL22):​c.462+242G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,014 control chromosomes in the GnomAD database, including 3,856 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 0.18 (3856 hom., cov: 32)
• Consequence: IL22 NM_020525.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 40 publications found

Genes affected

IL22 (HGNC:14900): (interleukin 22) This gene is a member of the IL10 family of cytokines that mediate cellular inflammatory responses. The encoded protein functions in antimicrobial defense at mucosal surfaces and in tissue repair. This protein also has pro-inflammatory properties and plays a role in in the pathogenesis of several intestinal diseases. The encoded protein is a crucial cytokine that regulates host immunity in infectious diseases, including COVID-19 (disease caused by SARS-CoV-2). [provided by RefSeq, Dec 2021]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL22	NM_020525.5	c.462+242G>C		intron_variant	Intron 5 of 5	ENST00000538666.6	NP_065386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL22	ENST00000538666.6	c.462+242G>C		intron_variant	Intron 5 of 5	1	NM_020525.5	ENSP00000442424.1
IL22	ENST00000328087.6	c.462+242G>C		intron_variant	Intron 4 of 4	1		ENSP00000329384.4

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27560 AN: 151896 Hom.: 3838 Cov.: 32

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.0569

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0801

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.182 AC: 27637 AN: 152014 Hom.: 3856 Cov.: 32 AF XY: 0.183 AC XY: 13570 AN XY: 74302

African (AFR) AF: 0.367 AC: 15203 AN: 41402

American (AMR) AF: 0.149 AC: 2269 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 496 AN: 3470

East Asian (EAS) AF: 0.327 AC: 1683 AN: 5152

South Asian (SAS) AF: 0.305 AC: 1469 AN: 4820

European-Finnish (FIN) AF: 0.0569 AC: 602 AN: 10578

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.0801 AC: 5445 AN: 67994

Other (OTH) AF: 0.178 AC: 376 AN: 2114

Alfa AF: 0.129 Hom.: 298

Bravo AF: 0.195

Asia WGS AF: 0.318 AC: 1100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.021
DANN	Benign	0.19
PhyloP100		-1.1
Mutation Taster		=100/0	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: rs1179251; hg19: chr12-68645051;