chr6-137004764-TAA-T

Variant names:

• chr6-137004764-TAA-T
• rs5880323
• NM_014432.4:c.725-6_725-5delTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014432.4(IL20RA):​c.725-6_725-5delTT variant causes a splice region, 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, 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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IL20RA	NM_014432.4	c.725-6_725-5delTT		splice_region_variant, intron_variant	Intron 5 of 6	ENST00000316649.10	NP_055247.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL20RA	ENST00000316649.10	c.725-6_725-5delTT		splice_region_variant, intron_variant	Intron 5 of 6	1	NM_014432.4	ENSP00000314976.5
IL20RA	ENST00000367748.4	c.392-6_392-5delTT		splice_region_variant, intron_variant	Intron 4 of 5	1		ENSP00000356722.1
IL20RA	ENST00000541547.5	c.578-6_578-5delTT		splice_region_variant, intron_variant	Intron 5 of 6	2		ENSP00000437843.1
IL20RA	ENST00000468393.5	c.392-6_392-5delTT		splice_region_variant, intron_variant	Intron 4 of 4	4		ENSP00000489177.1

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

GnomAD2 exomes AF: 0.443 AC: 67230 AN: 151602 AF XY: 0.449

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 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 AC: 3722 AN: 27554

Gnomad4 AMR exome AF: 0.454 AC: 12637 AN: 27816

Gnomad4 ASJ exome AF: 0.436 AC: 9404 AN: 21590

Gnomad4 EAS exome AF: 0.503 AC: 18319 AN: 36414

Gnomad4 SAS exome AF: 0.438 AC: 30567 AN: 69804

Gnomad4 FIN exome AF: 0.466 AC: 19659 AN: 42162

Gnomad4 NFE exome AF: 0.422 AC: 405777 AN: 960710

Gnomad4 Remaining exome AF: 0.416 AC: 21509 AN: 51674

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 AC: 0.12279 AN: 0.12279

Gnomad4 AMR AF: 0.486 AC: 0.485915 AN: 0.485915

Gnomad4 ASJ AF: 0.514 AC: 0.514252 AN: 0.514252

Gnomad4 EAS AF: 0.768 AC: 0.767533 AN: 0.767533

Gnomad4 SAS AF: 0.490 AC: 0.490065 AN: 0.490065

Gnomad4 FIN AF: 0.550 AC: 0.550259 AN: 0.550259

Gnomad4 NFE AF: 0.441 AC: 0.441234 AN: 0.441234

Gnomad4 OTH AF: 0.392 AC: 0.392224 AN: 0.392224

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Name	Calibrated prediction	Score	Prediction
Mutation Taster		=99/1	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

Publications

LitVar

Other links and lift over

dbSNP: rs5880323; hg19: chr6-137325901;