1-24121311-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_021258.4(IL22RA1):c.1219A>G(p.Met407Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00302 in 1,612,856 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.012 (31 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (33 hom.)
• Consequence: IL22RA1 NM_021258.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.69

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014988482).
• BP6: Variant 1-24121311-T-C is Benign according to our data. Variant chr1-24121311-T-C is described in ClinVar as [Benign]. Clinvar id is 775524.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0118 (1799/152212) while in subpopulation AFR AF= 0.0349 (1447/41518). AF 95% confidence interval is 0.0334. There are 31 homozygotes in gnomad4. There are 869 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL22RA1	NM_021258.4	c.1219A>G	p.Met407Val	missense_variant	7/7	ENST00000270800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL22RA1	ENST00000270800.2	c.1219A>G	p.Met407Val	missense_variant	7/7	1	NM_021258.4	P1

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1794 AN: 152094 Hom.: 31 Cov.: 32

Gnomad AFR AF: 0.0348

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0146

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00126

Gnomad OTH AF: 0.0143

GnomAD3 exomes AF: 0.00416 AC: 1042 AN: 250392 Hom.: 16 AF XY: 0.00337 AC XY: 456 AN XY: 135356

Gnomad AFR exome AF: 0.0334

Gnomad AMR exome AF: 0.00769

Gnomad ASJ exome AF: 0.000402

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000197

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00160

Gnomad OTH exome AF: 0.00705

GnomAD4 exome AF: 0.00210 AC: 3066 AN: 1460644 Hom.: 33 Cov.: 36 AF XY: 0.00195 AC XY: 1416 AN XY: 726450

Gnomad4 AFR exome AF: 0.0339

Gnomad4 AMR exome AF: 0.00872

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000984

Gnomad4 OTH exome AF: 0.00613

GnomAD4 genome AF: 0.0118 AC: 1799 AN: 152212 Hom.: 31 Cov.: 32 AF XY: 0.0117 AC XY: 869 AN XY: 74404

Gnomad4 AFR AF: 0.0349

Gnomad4 AMR AF: 0.0146

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00126

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00320 Hom.: 7

Bravo AF: 0.0146

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0313 AC: 138

ESP6500EA AF: 0.00198 AC: 17

ExAC AF: 0.00434 AC: 527

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.00147

EpiControl AF: 0.00285

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 31, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.0020
Dann	Benign	0.32
DEOGEN2	Benign	0.012	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0040	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.058
Sift	Benign	0.84	T
Sift4G	Benign	0.88	T
Polyphen		0.0	B
Vest4		0.014
MVP		0.092
MPC		0.11
ClinPred		0.0023	T
GERP RS		-8.7
Varity_R		0.035
gMVP		0.14

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: rs35401673; hg19: chr1-24447801;