rs1009639

chr5-55859574-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_139017.7(IL31RA):c.129C>T(p.Pro43=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 1,612,148 control chromosomes in the GnomAD database, including 418,680 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.70 (37265 hom., cov: 32)
  • Exomes 𝑓: 0.72 (381415 hom.)
• Consequence: IL31RA NM_139017.7 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.288

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-55859574-C-T is Benign according to our data. Variant chr5-55859574-C-T is described in ClinVar as [Benign]. Clinvar id is 1300053.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-55859574-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.288 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL31RA	NM_139017.7	c.129C>T	p.Pro43=	synonymous_variant	2/15	ENST00000652347.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL31RA	ENST00000652347.2	c.129C>T	p.Pro43=	synonymous_variant	2/15		NM_139017.7	A2

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105685 AN: 151948 Hom.: 37245 Cov.: 32

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.694

GnomAD3 exomes AF: 0.676 AC: 170006 AN: 251414 Hom.: 59806 AF XY: 0.692 AC XY: 94083 AN XY: 135876

Gnomad AFR exome AF: 0.660

Gnomad AMR exome AF: 0.424

Gnomad ASJ exome AF: 0.738

Gnomad EAS exome AF: 0.465

Gnomad SAS exome AF: 0.782

Gnomad FIN exome AF: 0.769

Gnomad NFE exome AF: 0.736

Gnomad OTH exome AF: 0.703

GnomAD4 exome AF: 0.719 AC: 1049850 AN: 1460080 Hom.: 381415 Cov.: 38 AF XY: 0.723 AC XY: 524905 AN XY: 726504

Gnomad4 AFR exome AF: 0.665

Gnomad4 AMR exome AF: 0.439

Gnomad4 ASJ exome AF: 0.745

Gnomad4 EAS exome AF: 0.495

Gnomad4 SAS exome AF: 0.781

Gnomad4 FIN exome AF: 0.768

Gnomad4 NFE exome AF: 0.732

Gnomad4 OTH exome AF: 0.718

GnomAD4 genome AF: 0.695 AC: 105761 AN: 152068 Hom.: 37265 Cov.: 32 AF XY: 0.696 AC XY: 51752 AN XY: 74340

Gnomad4 AFR AF: 0.671

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.736

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.782

Gnomad4 NFE AF: 0.737

Gnomad4 OTH AF: 0.697

Alfa AF: 0.714 Hom.: 50433

Bravo AF: 0.668

Asia WGS AF: 0.646 AC: 2249 AN: 3478

EpiCase AF: 0.739

EpiControl AF: 0.737

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Amyloidosis, primary localized cutaneous, 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.85
Dann	Benign	0.48

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: rs1009639; hg19: chr5-55155402; COSMIC: COSV51681840;