6-137004764-TAAAAAA-TAAA

Variant names:

• chr6-137004764-TAAA-T
• rs5880323
• NM_014432.4:c.725-7_725-5delTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014432.4(IL20RA):​c.725-7_725-5delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0387 in 1,386,042 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.00085 (0 hom., cov: 0)
  • Exomes 𝑓: 0.043 (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 2 ACMG points.

• PM2: Variant has high frequency in the EAS (0.128) population. However there is too low homozygotes in high coverage region: (expected more than 518, got 0).

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.725-7_725-5delTTT		splice_region intron	N/A	NP_055247.4
	IL20RA	NM_001278722.2		c.578-7_578-5delTTT		splice_region intron	N/A	NP_001265651.2	Q9UHF4-3
	IL20RA	NM_001278723.3		c.392-7_392-5delTTT		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.725-7_725-5delTTT		splice_region intron	N/A	ENSP00000314976.5	Q9UHF4-1
	IL20RA	ENST00000367748.4	TSL:1	c.392-7_392-5delTTT		splice_region intron	N/A	ENSP00000356722.1	Q9UHF4-2
	IL20RA	ENST00000878901.1		c.728-7_728-5delTTT		splice_region intron	N/A	ENSP00000548960.1

Frequencies

GnomAD3 genomes AF: 0.000850 AC: 124 AN: 145936 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000877

Gnomad ASJ AF: 0.000872

Gnomad EAS AF: 0.00118

Gnomad SAS AF: 0.000215

Gnomad FIN AF: 0.00509

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000840

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0689 AC: 10443 AN: 151602 AF XY: 0.0698

Gnomad AFR exome AF: 0.00694

Gnomad AMR exome AF: 0.103

Gnomad ASJ exome AF: 0.0862

Gnomad EAS exome AF: 0.148

Gnomad FIN exome AF: 0.0707

Gnomad NFE exome AF: 0.0579

Gnomad OTH exome AF: 0.0694

GnomAD4 exome AF: 0.0431 AC: 53469 AN: 1240060 Hom.: 0 AF XY: 0.0444 AC XY: 27385 AN XY: 617436

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

African (AFR) AF: 0.00637 AC: 180 AN: 28238

American (AMR) AF: 0.0860 AC: 2239 AN: 26024

Ashkenazi Jewish (ASJ) AF: 0.0616 AC: 1298 AN: 21080

East Asian (EAS) AF: 0.132 AC: 4231 AN: 32158

South Asian (SAS) AF: 0.0594 AC: 4120 AN: 69326

European-Finnish (FIN) AF: 0.0723 AC: 2984 AN: 41278

Middle Eastern (MID) AF: 0.0377 AC: 175 AN: 4640

European-Non Finnish (NFE) AF: 0.0372 AC: 35931 AN: 965816

Other (OTH) AF: 0.0449 AC: 2311 AN: 51500

⚠️ 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: 0.000849 AC: 124 AN: 145982 Hom.: 0 Cov.: 0 AF XY: 0.00110 AC XY: 78 AN XY: 70854

⚠️ 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: 39266

American (AMR) AF: 0.000877 AC: 13 AN: 14830

Ashkenazi Jewish (ASJ) AF: 0.000872 AC: 3 AN: 3440

East Asian (EAS) AF: 0.00118 AC: 6 AN: 5070

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

European-Finnish (FIN) AF: 0.00509 AC: 45 AN: 8842

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.000840 AC: 56 AN: 66678

Other (OTH) AF: 0.00 AC: 0 AN: 2032

⚠️ 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.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
Mutation Taster		=91/9	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;