Genetic Variant NM_014432.4:c.725-7_725-5delTTT (chr6-137004764-TAAA-T) – ACMG Classification: Uncertain_significance (2 pts)

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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00085 ( 0 hom., cov: 0)

Exomes 𝑓: 0.043 ( 0 hom. )

Consequence

IL20RA
NM_014432.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.60

Publications

2 publications found

Variant links:

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]

IL20RA links:

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ACMG classification

Classification was made for transcript

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL20RA	NM_014432.4 link	c.725-7_725-5delTTT		splice_region_variant, intron_variant	Intron 5 of 6	ENST00000316649.10	NP_055247.4	Q9UHF4-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL20RA	ENST00000316649.10 link	c.725-7_725-5delTTT	splice_region_variant, intron_variant	Intron 5 of 6	1	NM_014432.4	ENSP00000314976.5	Q9UHF4-1
IL20RA	ENST00000367748.4 link	c.392-7_392-5delTTT	splice_region_variant, intron_variant	Intron 4 of 5	1		ENSP00000356722.1	Q9UHF4-2
IL20RA	ENST00000541547.5 link	c.578-7_578-5delTTT	splice_region_variant, intron_variant	Intron 5 of 6	2		ENSP00000437843.1	Q9UHF4-3
IL20RA	ENST00000468393.5 link	c.392-7_392-5delTTT	splice_region_variant, intron_variant	Intron 4 of 4	4		ENSP00000489177.1	A0A0U1RQU9

Frequencies

GnomAD3 genomes

AF:

0.000850

AC:

124

AN:

145936

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0444

AC XY:

27385

AN XY:

617436

show subpopulations

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.274

Heterozygous variant carriers

5065

10130

15194

20259

25324

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

1160

2320

3480

4640

5800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000849

AC:

124

AN:

145982

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

70854

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

39266

American (AMR)

AF:

0.000877

AC:

AN:

14830

Ashkenazi Jewish (ASJ)

AF:

0.000872

AC:

AN:

3440

East Asian (EAS)

AF:

0.00118

AC:

AN:

5070

South Asian (SAS)

AF:

0.000216

AC:

AN:

4632

European-Finnish (FIN)

AF:

0.00509

AC:

AN:

8842

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.000840

AC:

AN:

66678

Other (OTH)

AF:

0.00

AC:

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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.309

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.6

Mutation Taster

=91/9

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over