Variant chr12-68251515-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020525.5(IL22):c.460A>G(p.Lys154Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000254 in 1,608,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

IL22
NM_020525.5 missense, splice_region

Scores

Splicing: ADA: 0.0002360

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0740

Variant links:

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]

IL22 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.031203657).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL22	NM_020525.5 linkuse as main transcript	c.460A>G	p.Lys154Glu	missense_variant, splice_region_variant	5/6	ENST00000538666.6	NP_065386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL22	ENST00000538666.6 linkuse as main transcript	c.460A>G	p.Lys154Glu	missense_variant, splice_region_variant	5/6	1	NM_020525.5	ENSP00000442424	P1
IL22	ENST00000328087.6 linkuse as main transcript	c.460A>G	p.Lys154Glu	missense_variant, splice_region_variant	4/5	1		ENSP00000329384	P1

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000255

AC:

AN:

250956

Hom.:

AF XY:

0.000236

AC XY:

AN XY:

135620

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.000608

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000194

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000246

AC:

359

AN:

1456404

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

185

AN XY:

724982

show subpopulations

Gnomad4 AFR exome

AF:

0.000629

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000264

Gnomad4 OTH exome

AF:

0.000233

GnomAD4 genome

AF:

0.000328

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000322

Hom.:

Bravo

AF:

0.000412

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000255

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000475

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2021

The c.460A>G (p.K154E) alteration is located in exon 4 (coding exon 4) of the IL22 gene. This alteration results from a A to G substitution at nucleotide position 460, causing the lysine (K) at amino acid position 154 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.60

DEOGEN2

Benign

0.19

T;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.56

.;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.031

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.6

D;D

REVEL

Benign

0.038

Sift

Benign

0.14

T;T

Sift4G

Benign

0.64

T;T

Polyphen

0.0020

B;B

Vest4

0.16

MVP

0.43

MPC

0.14

ClinPred

0.012

GERP RS

-0.52

Varity_R

0.40

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00024

dbscSNV1_RF

Benign

0.0060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over