6-137173485-G-A

Position:

• chr6-137173485-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052962.3(IL22RA2):​c.-138C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 152,134 control chromosomes in the GnomAD database, including 20,738 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 0.50 (20738 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: IL22RA2 NM_052962.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL22RA2	NM_052962.3	c.-138C>T		5_prime_UTR_variant	1/7	ENST00000296980.7	NP_443194.1
IL22RA2	NM_181309.2	c.-138C>T		5_prime_UTR_variant	1/6		NP_851826.1
IL22RA2	NM_181310.2	c.-138C>T		5_prime_UTR_variant	1/5		NP_851827.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL22RA2	ENST00000296980.7	c.-138C>T		5_prime_UTR_variant	1/7	1	NM_052962.3	ENSP00000296980
IL22RA2	ENST00000339602.3	c.-138C>T		5_prime_UTR_variant	1/5	1		ENSP00000340920
IL22RA2	ENST00000349184.9	c.-138C>T		5_prime_UTR_variant	1/6	1		ENSP00000296979	P1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76367 AN: 152014 Hom.: 20686 Cov.: 33

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.535

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 0.500

GnomAD4 genome AF: 0.503 AC: 76473 AN: 152132 Hom.: 20738 Cov.: 33 AF XY: 0.504 AC XY: 37451 AN XY: 74374

Gnomad4 AFR AF: 0.706

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.539

Alfa AF: 0.448 Hom.: 6556

Bravo AF: 0.522

Asia WGS AF: 0.612 AC: 2125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.59

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: rs6570136; hg19: chr6-137494622;