Genetic Variant NM_021258.4:c.355+58G>A (chr1-24137073-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_021258.4(IL22RA1):c.355+58G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,539,464 control chromosomes in the GnomAD database, including 38,224 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.23 ( 4191 hom., cov: 31)

Exomes 𝑓: 0.22 ( 34033 hom. )

Consequence

IL22RA1
NM_021258.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.977

Publications

6 publications found

Variant links:

Genes affected

IL22RA1 (HGNC:13700): (interleukin 22 receptor subunit alpha 1) The protein encoded by this gene belongs to the class II cytokine receptor family, and has been shown to be a receptor for interleukin 22 (IL22). IL22 receptor is a protein complex that consists of this protein and interleukin 10 receptor, beta (IL10BR/CRFB4), a subunit also shared by the receptor complex for interleukin 10 (IL10). This gene and interleukin 28 receptor, alpha (IL28RA) form a cytokine receptor gene cluster in the chromosomal region 1p36. [provided by RefSeq, Jul 2008]

IL22RA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 1-24137073-C-T is Benign according to our data. Variant chr1-24137073-C-T is described in ClinVar as Benign. ClinVar VariationId is 2688450.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL22RA1	NM_021258.4 link	c.355+58G>A		intron_variant	Intron 3 of 6	ENST00000270800.2	NP_067081.2	Q8N6P7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL22RA1	ENST00000270800.2 link	c.355+58G>A		intron_variant	Intron 3 of 6	1	NM_021258.4	ENSP00000270800.1		Q8N6P7

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34261

AN:

151918

Hom.:

4189

Cov.:

show subpopulations

Gnomad AFR

AF:

0.288

Gnomad AMI

AF:

0.214

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.285

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.247

Gnomad FIN

AF:

0.197

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.216

Gnomad OTH

AF:

0.218

GnomAD4 exome

AF:

0.215

AC:

298802

AN:

1387428

Hom.:

34033

AF XY:

0.217

AC XY:

148606

AN XY:

683452

show subpopulations

African (AFR)

AF:

0.292

AC:

9438

AN:

32336

American (AMR)

AF:

0.118

AC:

4973

AN:

42292

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

6701

AN:

24026

East Asian (EAS)

AF:

0.000831

AC:

AN:

38520

South Asian (SAS)

AF:

0.262

AC:

21021

AN:

80284

European-Finnish (FIN)

AF:

0.210

AC:

9808

AN:

46694

Middle Eastern (MID)

AF:

0.287

AC:

1545

AN:

5390

European-Non Finnish (NFE)

AF:

0.220

AC:

232830

AN:

1060516

Other (OTH)

AF:

0.217

AC:

12454

AN:

57370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

11171

22342

33512

44683

55854

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8156

16312

24468

32624

40780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.226

AC:

34293

AN:

152036

Hom.:

4191

Cov.:

AF XY:

0.223

AC XY:

16584

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.288

AC:

11935

AN:

41426

American (AMR)

AF:

0.175

AC:

2669

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

987

AN:

3468

East Asian (EAS)

AF:

0.00212

AC:

AN:

5186

South Asian (SAS)

AF:

0.248

AC:

1194

AN:

4812

European-Finnish (FIN)

AF:

0.197

AC:

2087

AN:

10590

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.216

AC:

14677

AN:

67966

Other (OTH)

AF:

0.215

AC:

454

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1311

2623

3934

5246

6557

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.216

Hom.:

6001

Bravo

AF:

0.222

Asia WGS

AF:

0.106

AC:

371

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 35% of patients studied by a panel of primary immunodeficiencies. Number of patients: 31. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.5

(source)

DANN

Benign

0.48

PhyloP100

-0.98

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over