chr12-68250838-T-A

Variant names:

• chr12-68250838-T-A
• rs1012356
• NM_020525.5:c.462+675A>T

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+675A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,996 control chromosomes in the GnomAD database, including 16,369 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 0.46 (16369 hom., cov: 31)
• Consequence: IL22 NM_020525.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 22 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL22	NM_020525.5	c.462+675A>T		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+675A>T		intron_variant	Intron 5 of 5	1	NM_020525.5	ENSP00000442424.1
IL22	ENST00000328087.6	c.462+675A>T		intron_variant	Intron 4 of 4	1		ENSP00000329384.4

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69894 AN: 151880 Hom.: 16344 Cov.: 31

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.460 AC: 69964 AN: 151996 Hom.: 16369 Cov.: 31 AF XY: 0.464 AC XY: 34488 AN XY: 74298

African (AFR) AF: 0.485 AC: 20084 AN: 41452

American (AMR) AF: 0.474 AC: 7237 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1969 AN: 3472

East Asian (EAS) AF: 0.519 AC: 2672 AN: 5152

South Asian (SAS) AF: 0.609 AC: 2936 AN: 4822

European-Finnish (FIN) AF: 0.465 AC: 4912 AN: 10558

Middle Eastern (MID) AF: 0.606 AC: 177 AN: 292

European-Non Finnish (NFE) AF: 0.419 AC: 28496 AN: 67940

Other (OTH) AF: 0.505 AC: 1068 AN: 2114

Alfa AF: 0.278 Hom.: 682

Bravo AF: 0.464

Asia WGS AF: 0.592 AC: 2055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.044
DANN	Benign	0.41
PhyloP100		-1.0
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: rs1012356; hg19: chr12-68644618;