6-137004764-TAAAAAA-TAA

Variant names:

• chr6-137004764-TAAAA-T
• rs5880323
• NM_014432.4:c.725-8_725-5delTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_014432.4(IL20RA):​c.725-8_725-5delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00072 in 1,437,352 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000068 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00080 (0 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014432.4. 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
	IL20RA	NM_014432.4	MANE Select	c.725-8_725-5delTTTT		splice_region intron	N/A	NP_055247.4
	IL20RA	NM_001278722.2		c.578-8_578-5delTTTT		splice_region intron	N/A	NP_001265651.2	Q9UHF4-3
	IL20RA	NM_001278723.3		c.392-8_392-5delTTTT		splice_region intron	N/A	NP_001265652.2	Q9UHF4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL20RA	ENST00000316649.10	TSL:1 MANE Select	c.725-8_725-5delTTTT		splice_region intron	N/A	ENSP00000314976.5	Q9UHF4-1
	IL20RA	ENST00000367748.4	TSL:1	c.392-8_392-5delTTTT		splice_region intron	N/A	ENSP00000356722.1	Q9UHF4-2
	IL20RA	ENST00000878901.1		c.728-8_728-5delTTTT		splice_region intron	N/A	ENSP00000548960.1

Frequencies

GnomAD3 genomes AF: 0.00000685 AC: 1 AN: 146030 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00191 AC: 289 AN: 151602 AF XY: 0.00197

Gnomad AFR exome AF: 0.000176

Gnomad AMR exome AF: 0.00254

Gnomad ASJ exome AF: 0.00287

Gnomad EAS exome AF: 0.00475

Gnomad FIN exome AF: 0.00250

Gnomad NFE exome AF: 0.00132

Gnomad OTH exome AF: 0.00260

GnomAD4 exome AF: 0.000801 AC: 1034 AN: 1291322 Hom.: 0 AF XY: 0.000833 AC XY: 536 AN XY: 643544

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

African (AFR) AF: 0.000140 AC: 4 AN: 28488

American (AMR) AF: 0.00237 AC: 67 AN: 28292

Ashkenazi Jewish (ASJ) AF: 0.00109 AC: 24 AN: 22086

East Asian (EAS) AF: 0.00288 AC: 104 AN: 36092

South Asian (SAS) AF: 0.00150 AC: 109 AN: 72448

European-Finnish (FIN) AF: 0.00176 AC: 76 AN: 43252

Middle Eastern (MID) AF: 0.000209 AC: 1 AN: 4774

European-Non Finnish (NFE) AF: 0.000607 AC: 608 AN: 1002316

Other (OTH) AF: 0.000765 AC: 41 AN: 53574

⚠️ 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: 0.00000685 AC: 1 AN: 146030 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 70848

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

African (AFR) AF: 0.00 AC: 0 AN: 39192

American (AMR) AF: 0.00 AC: 0 AN: 14824

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5086

South Asian (SAS) AF: 0.00 AC: 0 AN: 4652

European-Finnish (FIN) AF: 0.000113 AC: 1 AN: 8866

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66736

Other (OTH) AF: 0.00 AC: 0 AN: 2016

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;