5-55853555-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000490985.5(IL31RA):c.-520C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00646 in 1,550,846 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0046 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0067 (42 hom.)
• Consequence: IL31RA ENST00000490985.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.372

Genes affected

IL31RA (HGNC:18969): (interleukin 31 receptor A) The protein encoded by this gene belongs to the type I cytokine receptor family. This receptor, with homology to gp130, is expressed on monocytes, and is involved in IL-31 signaling via activation of STAT-3 and STAT-5. It functions either as a monomer, or as part of a receptor complex with oncostatin M receptor (OSMR). Several alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Jun 2011]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 5-55853555-C-T is Benign according to our data. Variant chr5-55853555-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2655465.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 695 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL31RA	NM_139017.7	c.63+1922C>T		intron_variant		ENST00000652347.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL31RA	ENST00000652347.2	c.63+1922C>T		intron_variant			NM_139017.7	A2

Frequencies

GnomAD3 genomes AF: 0.00457 AC: 695 AN: 152214 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00508

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00835

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00419 AC: 633 AN: 151102 Hom.: 4 AF XY: 0.00422 AC XY: 341 AN XY: 80822

Gnomad AFR exome AF: 0.000834

Gnomad AMR exome AF: 0.000487

Gnomad ASJ exome AF: 0.00166

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000222

Gnomad FIN exome AF: 0.00787

Gnomad NFE exome AF: 0.00800

Gnomad OTH exome AF: 0.00295

GnomAD4 exome AF: 0.00666 AC: 9318 AN: 1398514 Hom.: 42 Cov.: 31 AF XY: 0.00645 AC XY: 4450 AN XY: 689736

Gnomad4 AFR exome AF: 0.000855

Gnomad4 AMR exome AF: 0.000532

Gnomad4 ASJ exome AF: 0.00155

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000265

Gnomad4 FIN exome AF: 0.00787

Gnomad4 NFE exome AF: 0.00795

Gnomad4 OTH exome AF: 0.00433

GnomAD4 genome AF: 0.00456 AC: 695 AN: 152332 Hom.: 1 Cov.: 33 AF XY: 0.00415 AC XY: 309 AN XY: 74492

Gnomad4 AFR AF: 0.00115

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00508

Gnomad4 NFE AF: 0.00835

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00664 Hom.: 2

Bravo AF: 0.00405

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

IL31RA: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	7.7
Dann	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs190185736; hg19: chr5-55149383;