rs16884641

Positions:

• chr5-55916618-T-A
• chr5-55916618-T-C
• chr5-55916618-T-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_139017.7(IL31RA):​c.1819-26T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0057 in 1,603,294 control chromosomes in the GnomAD database, including 36 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 0.0038 (3 hom., cov: 31)
  • Exomes 𝑓: 0.0059 (33 hom.)
• Consequence: IL31RA NM_139017.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.476

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS2: High AC in GnomAd4 at 579 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL31RA	NM_139017.7	c.1819-26T>A		intron_variant		ENST00000652347.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL31RA	ENST00000652347.2	c.1819-26T>A		intron_variant			NM_139017.7	A2

Frequencies

GnomAD3 genomes AF: 0.00381 AC: 579 AN: 151942 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.000942

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00331

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00660

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00347 AC: 872 AN: 251254 Hom.: 2 AF XY: 0.00370 AC XY: 503 AN XY: 135820

Gnomad AFR exome AF: 0.000985

Gnomad AMR exome AF: 0.00254

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000523

Gnomad FIN exome AF: 0.00356

Gnomad NFE exome AF: 0.00578

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00590 AC: 8562 AN: 1451234 Hom.: 33 Cov.: 30 AF XY: 0.00582 AC XY: 4206 AN XY: 722674

Gnomad4 AFR exome AF: 0.000931

Gnomad4 AMR exome AF: 0.00271

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000686

Gnomad4 FIN exome AF: 0.00427

Gnomad4 NFE exome AF: 0.00707

Gnomad4 OTH exome AF: 0.00541

GnomAD4 genome AF: 0.00381 AC: 579 AN: 152060 Hom.: 3 Cov.: 31 AF XY: 0.00346 AC XY: 257 AN XY: 74322

Gnomad4 AFR AF: 0.000940

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00331

Gnomad4 NFE AF: 0.00661

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.000209 Hom.: 9175

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.6
DANN	Benign	0.62

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: rs16884641; hg19: chr5-55212446;