12-68252741-T-C

Position:

• chr12-68252741-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000538666.6(IL22):​c.252+23A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 1,611,750 control chromosomes in the GnomAD database, including 271,208 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 0.58 (26049 hom., cov: 31)
  • Exomes 𝑓: 0.58 (245159 hom.)
• Consequence: IL22 ENST00000538666.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL22	NM_020525.5	c.252+23A>G		intron_variant		ENST00000538666.6	NP_065386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL22	ENST00000538666.6	c.252+23A>G		intron_variant		1	NM_020525.5	ENSP00000442424	P1
IL22	ENST00000328087.6	c.252+23A>G		intron_variant		1		ENSP00000329384	P1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88431 AN: 151854 Hom.: 26023 Cov.: 31

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.538

GnomAD3 exomes AF: 0.547 AC: 137220 AN: 250714 Hom.: 38106 AF XY: 0.541 AC XY: 73319 AN XY: 135480

Gnomad AFR exome AF: 0.633

Gnomad AMR exome AF: 0.526

Gnomad ASJ exome AF: 0.471

Gnomad EAS exome AF: 0.498

Gnomad SAS exome AF: 0.450

Gnomad FIN exome AF: 0.550

Gnomad NFE exome AF: 0.583

Gnomad OTH exome AF: 0.539

GnomAD4 exome AF: 0.576 AC: 841420 AN: 1459778 Hom.: 245159 Cov.: 33 AF XY: 0.571 AC XY: 414565 AN XY: 726348

Gnomad4 AFR exome AF: 0.630

Gnomad4 AMR exome AF: 0.523

Gnomad4 ASJ exome AF: 0.478

Gnomad4 EAS exome AF: 0.455

Gnomad4 SAS exome AF: 0.453

Gnomad4 FIN exome AF: 0.554

Gnomad4 NFE exome AF: 0.596

Gnomad4 OTH exome AF: 0.559

GnomAD4 genome AF: 0.582 AC: 88492 AN: 151972 Hom.: 26049 Cov.: 31 AF XY: 0.577 AC XY: 42855 AN XY: 74258

Gnomad4 AFR AF: 0.635

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.482

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.534

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.532

Alfa AF: 0.569 Hom.: 25869

Bravo AF: 0.583

Asia WGS AF: 0.436 AC: 1519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.26

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: rs2227491; hg19: chr12-68646521; COSMIC: COSV60159723;