5-55851624-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_139017.7(IL31RA):c.54G>A(p.Pro18=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00829 in 1,613,812 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0062 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0085 (69 hom.)
• Consequence: IL31RA NM_139017.7 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.04

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-55851624-G-A is Benign according to our data. Variant chr5-55851624-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 790791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.04 with no splicing effect.
• BS2: High AC in GnomAd at 941 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL31RA	NM_139017.7	c.54G>A	p.Pro18=	synonymous_variant	1/15	ENST00000652347.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL31RA	ENST00000652347.2	c.54G>A	p.Pro18=	synonymous_variant	1/15		NM_139017.7	A2

Frequencies

GnomAD3 genomes AF: 0.00619 AC: 941 AN: 152070 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00169

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000831

Gnomad FIN AF: 0.0139

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00960

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00685 AC: 1685 AN: 246130 Hom.: 12 AF XY: 0.00680 AC XY: 910 AN XY: 133804

Gnomad AFR exome AF: 0.00155

Gnomad AMR exome AF: 0.00293

Gnomad ASJ exome AF: 0.00618

Gnomad EAS exome AF: 0.000167

Gnomad SAS exome AF: 0.00124

Gnomad FIN exome AF: 0.0149

Gnomad NFE exome AF: 0.00991

Gnomad OTH exome AF: 0.00748

GnomAD4 exome AF: 0.00851 AC: 12432 AN: 1461624 Hom.: 69 Cov.: 31 AF XY: 0.00824 AC XY: 5988 AN XY: 727126

Gnomad4 AFR exome AF: 0.00176

Gnomad4 AMR exome AF: 0.00320

Gnomad4 ASJ exome AF: 0.00486

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.000881

Gnomad4 FIN exome AF: 0.0145

Gnomad4 NFE exome AF: 0.00978

Gnomad4 OTH exome AF: 0.00596

GnomAD4 genome AF: 0.00618 AC: 941 AN: 152188 Hom.: 3 Cov.: 32 AF XY: 0.00622 AC XY: 463 AN XY: 74412

Gnomad4 AFR AF: 0.00169

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00547

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000832

Gnomad4 FIN AF: 0.0139

Gnomad4 NFE AF: 0.00960

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00872 Hom.: 7

Bravo AF: 0.00534

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00813

EpiControl AF: 0.00913

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	IL31RA: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.9
Dann	Benign	0.71

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: rs140079651; hg19: chr5-55147452; COSMIC: COSV51683306; COSMIC: COSV51683306;