6-137004764-TAA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014432.4(IL20RA):c.725-6_725-5del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (12445 hom., cov: 0)
  • Exomes 𝑓: 0.42 (9676 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL20RA NM_014432.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.60

Genes affected

IL20RA (HGNC:6003): (interleukin 20 receptor subunit alpha) This gene encodes a member of the type II cytokine receptor family. The encoded protein is a subunit of the receptor for interleukin 20, a cytokine that may be involved in epidermal function. The interleukin 20 receptor is a heterodimeric complex consisting of the encoded protein and interleukin 20 receptor beta. This gene and interleukin 20 receptor beta are highly expressed in skin, and are upregulated in psoriasis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 6-137004764-TAA-T is Benign according to our data. Variant chr6-137004764-TAA-T is described in ClinVar as [Benign]. Clinvar id is 402973.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL20RA	NM_014432.4	c.725-6_725-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000316649.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL20RA	ENST00000316649.10	c.725-6_725-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_014432.4	P1
IL20RA	ENST00000367748.4	c.392-6_392-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1
IL20RA	ENST00000468393.5	c.392-6_392-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		4
IL20RA	ENST00000541547.5	c.578-6_578-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.381 AC: 55611 AN: 145974 Hom.: 12458 Cov.: 0

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.426

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.392

GnomAD3 exomes AF: 0.443 AC: 67230 AN: 151602 Hom.: 2410 AF XY: 0.449 AC XY: 37519 AN XY: 83602

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.464

Gnomad ASJ exome AF: 0.450

Gnomad EAS exome AF: 0.522

Gnomad SAS exome AF: 0.450

Gnomad FIN exome AF: 0.492

Gnomad NFE exome AF: 0.462

Gnomad OTH exome AF: 0.443

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.421 AC: 523531 AN: 1242372 Hom.: 9676 AF XY: 0.423 AC XY: 261743 AN XY: 618700

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.454

Gnomad4 ASJ exome AF: 0.436

Gnomad4 EAS exome AF: 0.503

Gnomad4 SAS exome AF: 0.438

Gnomad4 FIN exome AF: 0.466

Gnomad4 NFE exome AF: 0.422

Gnomad4 OTH exome AF: 0.416

GnomAD4 genome AF: 0.381 AC: 55582 AN: 146022 Hom.: 12445 Cov.: 0 AF XY: 0.392 AC XY: 27769 AN XY: 70872

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.768

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.392

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

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: rs5880323; hg19: chr6-137325901;