6-137004764-TAAAAAA-TAAAAAAA

Variant names:

• chr6-137004764-T-TA
• rs5880323
• NM_014432.4:c.725-5dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_014432.4(IL20RA):​c.725-5dupT 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.046 (498 hom., cov: 0)
  • Exomes 𝑓: 0.0046 (2 hom.)
• Consequence: IL20RA NM_014432.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60
• Publications: 2 publications found

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0457 AC: 6666 AN: 145978 Hom.: 497 Cov.: 0

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000215

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.000764

Gnomad OTH AF: 0.0312

GnomAD2 exomes AF: 0.0126 AC: 1913 AN: 151602 AF XY: 0.00949

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.00801

Gnomad ASJ exome AF: 0.000898

Gnomad EAS exome AF: 0.0000990

Gnomad FIN exome AF: 0.0000806

Gnomad NFE exome AF: 0.000949

Gnomad OTH exome AF: 0.00463

GnomAD4 exome AF: 0.00456 AC: 5904 AN: 1294468 Hom.: 2 Cov.: 0 AF XY: 0.00416 AC XY: 2682 AN XY: 645320

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.152 AC: 4251 AN: 27896

American (AMR) AF: 0.00753 AC: 214 AN: 28432

Ashkenazi Jewish (ASJ) AF: 0.000676 AC: 15 AN: 22196

East Asian (EAS) AF: 0.000164 AC: 6 AN: 36670

South Asian (SAS) AF: 0.000881 AC: 64 AN: 72664

European-Finnish (FIN) AF: 0.000138 AC: 6 AN: 43556

Middle Eastern (MID) AF: 0.00918 AC: 44 AN: 4794

European-Non Finnish (NFE) AF: 0.000814 AC: 818 AN: 1004628

Other (OTH) AF: 0.00906 AC: 486 AN: 53632

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0458 AC: 6685 AN: 146026 Hom.: 498 Cov.: 0 AF XY: 0.0444 AC XY: 3144 AN XY: 70880

African (AFR) AF: 0.162 AC: 6358 AN: 39216

American (AMR) AF: 0.0141 AC: 209 AN: 14834

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3440

East Asian (EAS) AF: 0.00 AC: 0 AN: 5074

South Asian (SAS) AF: 0.000216 AC: 1 AN: 4632

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8870

Middle Eastern (MID) AF: 0.0104 AC: 3 AN: 288

European-Non Finnish (NFE) AF: 0.000764 AC: 51 AN: 66732

Other (OTH) AF: 0.0310 AC: 63 AN: 2034

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs5880323; hg19: chr6-137325901;