rs6873519

chr5-55882919-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139017.7(IL31RA):c.455-125A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 858,518 control chromosomes in the GnomAD database, including 27,404 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (4117 hom., cov: 31)
  • Exomes 𝑓: 0.25 (23287 hom.)
• Consequence: IL31RA NM_139017.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL31RA	NM_139017.7	c.455-125A>C		intron_variant		ENST00000652347.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL31RA	ENST00000652347.2	c.455-125A>C		intron_variant			NM_139017.7	A2

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32969 AN: 151896 Hom.: 4119 Cov.: 31

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.213

GnomAD4 exome AF: 0.250 AC: 176522 AN: 706504 Hom.: 23287 AF XY: 0.249 AC XY: 93382 AN XY: 375148

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.335

Gnomad4 ASJ exome AF: 0.243

Gnomad4 EAS exome AF: 0.397

Gnomad4 SAS exome AF: 0.251

Gnomad4 FIN exome AF: 0.278

Gnomad4 NFE exome AF: 0.236

Gnomad4 OTH exome AF: 0.242

GnomAD4 genome AF: 0.217 AC: 32973 AN: 152014 Hom.: 4117 Cov.: 31 AF XY: 0.224 AC XY: 16614 AN XY: 74308

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.214

Alfa AF: 0.232 Hom.: 5542

Bravo AF: 0.215

Asia WGS AF: 0.327 AC: 1137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	12
Dann	Benign	0.69

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: rs6873519; hg19: chr5-55178747;