5-55913344-G-A

Position:

• chr5-55913344-G-A

Variant summary

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

The NM_139017.7(IL31RA):​c.1643-133G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 708,604 control chromosomes in the GnomAD database, including 27,446 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 0.23 (4810 hom., cov: 32)
  • Exomes 𝑓: 0.28 (22636 hom.)
• Consequence: IL31RA NM_139017.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.925

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL31RA	NM_139017.7	c.1643-133G>A		intron_variant		ENST00000652347.2	NP_620586.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL31RA	ENST00000652347.2	c.1643-133G>A		intron_variant			NM_139017.7	ENSP00000498630.1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 35008 AN: 151936 Hom.: 4813 Cov.: 32

Gnomad AFR AF: 0.0856

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.232

GnomAD4 exome AF: 0.277 AC: 154222 AN: 556550 Hom.: 22636 AF XY: 0.278 AC XY: 83261 AN XY: 299378

Gnomad4 AFR exome AF: 0.0817

Gnomad4 AMR exome AF: 0.339

Gnomad4 ASJ exome AF: 0.336

Gnomad4 EAS exome AF: 0.430

Gnomad4 SAS exome AF: 0.299

Gnomad4 FIN exome AF: 0.295

Gnomad4 NFE exome AF: 0.257

Gnomad4 OTH exome AF: 0.272

GnomAD4 genome AF: 0.230 AC: 35015 AN: 152054 Hom.: 4810 Cov.: 32 AF XY: 0.238 AC XY: 17693 AN XY: 74322

Gnomad4 AFR AF: 0.0857

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.233

Alfa AF: 0.0971 Hom.: 172

Bravo AF: 0.226

Asia WGS AF: 0.343 AC: 1192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.96
DANN	Benign	0.38

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: rs12153724; hg19: chr5-55209172; COSMIC: COSV51682300; COSMIC: COSV51682300;