chr6-137154721-T-C

Variant names:

• chr6-137154721-T-C
• rs7774349
• NM_052962.3:c.472+220A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052962.3(IL22RA2):​c.472+220A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,014 control chromosomes in the GnomAD database, including 29,221 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 0.60 (29221 hom., cov: 31)
• Consequence: IL22RA2 NM_052962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.752
• Publications: 7 publications found

Genes affected

IL22RA2 (HGNC:14901): (interleukin 22 receptor subunit alpha 2) This gene encodes a member of the class II cytokine receptor family. The encoded soluble protein specifically binds to and inhibits interleukin 22 activity by blocking the interaction of interleukin 22 with its cell surface receptor. The encoded protein may be important in the regulation of inflammatory response, and has been implicated in the regulation of tumorigenesis in the colon. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052962.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL22RA2	NM_052962.3	MANE Select	c.472+220A>G		intron	N/A	NP_443194.1	Q969J5-1
	IL22RA2	NM_181309.2		c.376+220A>G		intron	N/A	NP_851826.1	Q969J5-2
	IL22RA2	NM_181310.2		c.376+220A>G		intron	N/A	NP_851827.1	Q969J5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL22RA2	ENST00000296980.7	TSL:1 MANE Select	c.472+220A>G		intron	N/A	ENSP00000296980.2	Q969J5-1
	IL22RA2	ENST00000349184.9	TSL:1	c.376+220A>G		intron	N/A	ENSP00000296979.4	Q969J5-2
	IL22RA2	ENST00000339602.3	TSL:1	c.376+220A>G		intron	N/A	ENSP00000340920.3	Q969J5-3

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90430 AN: 151896 Hom.: 29160 Cov.: 31

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.596 AC: 90542 AN: 152014 Hom.: 29221 Cov.: 31 AF XY: 0.593 AC XY: 44087 AN XY: 74286

African (AFR) AF: 0.854 AC: 35424 AN: 41458

American (AMR) AF: 0.505 AC: 7715 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2117 AN: 3468

East Asian (EAS) AF: 0.726 AC: 3756 AN: 5170

South Asian (SAS) AF: 0.644 AC: 3103 AN: 4818

European-Finnish (FIN) AF: 0.421 AC: 4436 AN: 10544

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32173 AN: 67960

Other (OTH) AF: 0.638 AC: 1347 AN: 2110

Alfa AF: 0.520 Hom.: 87309

Bravo AF: 0.613

Asia WGS AF: 0.735 AC: 2554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.038
DANN	Benign	0.39
PhyloP100		-0.75
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: rs7774349; hg19: chr6-137475858;