chr12-68248867-T-C

Position:

• chr12-68248867-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_020525.5(IL22):​c.472A>G​(p.Ser158Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,612,194 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0074 (10 hom., cov: 32)
  • Exomes 𝑓: 0.00079 (10 hom.)
• Consequence: IL22 NM_020525.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.691

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0072984397).
• BP6: Variant 12-68248867-T-C is Benign according to our data. Variant chr12-68248867-T-C is described in ClinVar as [Benign]. Clinvar id is 709289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00735 (1120/152298) while in subpopulation AFR AF= 0.0256 (1062/41556). AF 95% confidence interval is 0.0243. There are 10 homozygotes in gnomad4. There are 511 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL22	NM_020525.5	c.472A>G	p.Ser158Gly	missense_variant	6/6	ENST00000538666.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL22	ENST00000538666.6	c.472A>G	p.Ser158Gly	missense_variant	6/6	1	NM_020525.5	P1
IL22	ENST00000328087.6	c.472A>G	p.Ser158Gly	missense_variant	5/5	1		P1

Frequencies

GnomAD3 genomes AF: 0.00734 AC: 1117 AN: 152180 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0256

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00196 AC: 491 AN: 250240 Hom.: 6 AF XY: 0.00135 AC XY: 183 AN XY: 135236

Gnomad AFR exome AF: 0.0259

Gnomad AMR exome AF: 0.00157

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000619

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.000795 AC: 1160 AN: 1459896 Hom.: 10 Cov.: 28 AF XY: 0.000695 AC XY: 505 AN XY: 726422

Gnomad4 AFR exome AF: 0.0277

Gnomad4 AMR exome AF: 0.00188

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000252

Gnomad4 OTH exome AF: 0.00171

GnomAD4 genome AF: 0.00735 AC: 1120 AN: 152298 Hom.: 10 Cov.: 32 AF XY: 0.00686 AC XY: 511 AN XY: 74460

Gnomad4 AFR AF: 0.0256

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.00174 Hom.: 4

Bravo AF: 0.00836

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0245 AC: 108

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00245 AC: 298

Asia WGS AF: 0.00173 AC: 6 AN: 3476

EpiCase AF: 0.00

EpiControl AF: 0.0000595

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.32	T;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.50	.;T
MetaRNN	Benign	0.0073	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.047
Sift	Benign	0.085	T;T
Sift4G	Benign	0.47	T;T
Polyphen		0.16	B;B
Vest4		0.073
MVP		0.49
MPC		0.090
ClinPred		0.0094	T
GERP RS		2.6
Varity_R		0.26
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2227507; hg19: chr12-68642647; COSMIC: COSV99075194;