Variant chr5-55910616-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

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. 13/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.30 ( 7183 hom., cov: 32)

Exomes 𝑓: 0.30 ( 67898 hom. )

Consequence

IL31RA
NM_139017.7 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.327

Variant links:

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]

IL31RA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 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 no_assertion_criteria_provided, 0 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 linkuse as main transcript	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 linkuse as main transcript	c.1586G>A	p.Ser529Asn	missense_variant	12/15		NM_139017.7	A2	Q8NI17-2

Frequencies

GnomAD3 genomes

AF:

0.303

AC:

46112

AN:

151972

Hom.:

7185

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.304

AC XY:

220815

AN XY:

726980

show subpopulations

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.:

AF XY:

0.300

AC XY:

22322

AN XY:

74358

show subpopulations

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: no assertion criteria provided

LINK: link

Submissions by phenotype

IL31RA-related disorder

Benign:1

Benign, no assertion criteria provided

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

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.25

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.034

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.62

.;T;T;T;T;T

MetaRNN

Benign

0.0014

T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

0.046

P;P;P;P;P

PrimateAI

Benign

0.33

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over