rs161704

chr5-55910616-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_139017.7(IL31RA):c.1586G>A(p.Ser529Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,613,250 control chromosomes in the GnomAD database, including 75,081 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7183 hom., cov: 32)
  • Exomes 𝑓: 0.30 (67898 hom.)
• Consequence: IL31RA NM_139017.7 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.327

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013931394).
• BP6: Variant 5-55910616-G-A is Benign according to our data. Variant chr5-55910616-G-A is described in ClinVar as [Benign]. Clinvar id is 3060128.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-55910616-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL31RA	NM_139017.7	c.1586G>A	p.Ser529Asn	missense_variant	12/15	ENST00000652347.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL31RA	ENST00000652347.2	c.1586G>A	p.Ser529Asn	missense_variant	12/15		NM_139017.7	A2

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46112 AN: 151972 Hom.: 7185 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.281

GnomAD3 exomes AF: 0.293 AC: 73677 AN: 251458 Hom.: 11284 AF XY: 0.297 AC XY: 40348 AN XY: 135902

Gnomad AFR exome AF: 0.343

Gnomad AMR exome AF: 0.191

Gnomad ASJ exome AF: 0.217

Gnomad EAS exome AF: 0.327

Gnomad SAS exome AF: 0.364

Gnomad FIN exome AF: 0.282

Gnomad NFE exome AF: 0.303

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.302 AC: 441483 AN: 1461160 Hom.: 67898 Cov.: 35 AF XY: 0.304 AC XY: 220815 AN XY: 726980

Gnomad4 AFR exome AF: 0.341

Gnomad4 AMR exome AF: 0.198

Gnomad4 ASJ exome AF: 0.215

Gnomad4 EAS exome AF: 0.374

Gnomad4 SAS exome AF: 0.362

Gnomad4 FIN exome AF: 0.287

Gnomad4 NFE exome AF: 0.302

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.303 AC: 46137 AN: 152090 Hom.: 7183 Cov.: 32 AF XY: 0.300 AC XY: 22322 AN XY: 74358

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.286

Alfa AF: 0.296 Hom.: 17520

Bravo AF: 0.299

TwinsUK AF: 0.316 AC: 1170

ALSPAC AF: 0.309 AC: 1190

ESP6500AA AF: 0.343 AC: 1511

ESP6500EA AF: 0.291 AC: 2503

ExAC AF: 0.301 AC: 36588

Asia WGS AF: 0.345 AC: 1200 AN: 3478

EpiCase AF: 0.286

EpiControl AF: 0.289

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

IL31RA-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 22, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	17
Dann	Benign	0.25
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.034
FATHMM_MKL	Benign	0.51	D
MetaRNN	Benign	0.0014	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	0.046	P;P;P;P;P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.10	N;N;N;N;.;N
REVEL	Benign	0.10
Sift	Benign	1.0	T;T;T;T;.;T
Sift4G	Benign	0.24	T;T;T;T;T;T
Polyphen		0.14	B;B;B;B;.;.
Vest4		0.050
MPC		0.11
ClinPred		0.0049	T
GERP RS		3.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs161704; hg19: chr5-55206444; COSMIC: COSV51679047; COSMIC: COSV51679047;