6-137004764-TAAAAAA-TAAAAA

Variant names:

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

Variant summary

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

The NM_014432.4(IL20RA):​c.725-5delT 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 0.48 (16872 hom., cov: 0)
  • Exomes 𝑓: 0.42 (4758 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
• 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 -10 ACMG points.

• BP6: Variant 6-137004764-TA-T is Benign according to our data. Variant chr6-137004764-TA-T is described in ClinVar as Benign. ClinVar VariationId is 402974.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.479 AC: 69737 AN: 145710 Hom.: 16870 Cov.: 0

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.489

GnomAD2 exomes AF: 0.406 AC: 61501 AN: 151602 AF XY: 0.409

Gnomad AFR exome AF: 0.361

Gnomad AMR exome AF: 0.363

Gnomad ASJ exome AF: 0.388

Gnomad EAS exome AF: 0.299

Gnomad FIN exome AF: 0.389

Gnomad NFE exome AF: 0.436

Gnomad OTH exome AF: 0.410

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.421 AC: 522335 AN: 1239266 Hom.: 4758 Cov.: 0 AF XY: 0.421 AC XY: 259762 AN XY: 617592

African (AFR) AF: 0.338 AC: 9365 AN: 27696

American (AMR) AF: 0.338 AC: 9188 AN: 27200

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 8209 AN: 21038

East Asian (EAS) AF: 0.264 AC: 8777 AN: 33186

South Asian (SAS) AF: 0.408 AC: 28175 AN: 69106

European-Finnish (FIN) AF: 0.378 AC: 15608 AN: 41278

Middle Eastern (MID) AF: 0.428 AC: 1972 AN: 4612

European-Non Finnish (NFE) AF: 0.436 AC: 419938 AN: 963680

Other (OTH) AF: 0.410 AC: 21103 AN: 51470

GnomAD4 genome AF: 0.479 AC: 69759 AN: 145756 Hom.: 16872 Cov.: 0 AF XY: 0.470 AC XY: 33233 AN XY: 70726

African (AFR) AF: 0.401 AC: 15739 AN: 39216

American (AMR) AF: 0.454 AC: 6720 AN: 14786

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1588 AN: 3440

East Asian (EAS) AF: 0.229 AC: 1161 AN: 5068

South Asian (SAS) AF: 0.506 AC: 2334 AN: 4614

European-Finnish (FIN) AF: 0.432 AC: 3807 AN: 8808

Middle Eastern (MID) AF: 0.528 AC: 151 AN: 286

European-Non Finnish (NFE) AF: 0.552 AC: 36759 AN: 66604

Other (OTH) AF: 0.486 AC: 986 AN: 2028

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
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV57357649; COSMIC: COSV57357649;