Genetic Variant IL31RA:p.Gly483Gly (chr5-55908359-T-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_139017.7(IL31RA):c.1449T>G(p.Gly483Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,613,758 control chromosomes in the GnomAD database, including 21,393 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1609 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19784 hom. )

Consequence

IL31RA
NM_139017.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.612

Publications

16 publications found

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 Gene-Disease associations (from GenCC):

familial primary localized cutaneous amyloidosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
amyloidosis, primary localized cutaneous, 2
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

IL31RA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 5-55908359-T-G is Benign according to our data. Variant chr5-55908359-T-G is described in ClinVar as Benign. ClinVar VariationId is 1098854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.612 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139017.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IL31RA	NM_139017.7	MANE Select	c.1449T>G	p.Gly483Gly	synonymous	Exon 11 of 15	NP_620586.3
IL31RA	NM_001242636.2		c.1392T>G	p.Gly464Gly	synonymous	Exon 11 of 15	NP_001229565.1
IL31RA	NM_001242637.2		c.1449T>G	p.Gly483Gly	synonymous	Exon 11 of 16	NP_001229566.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IL31RA	ENST00000652347.2	MANE Select	c.1449T>G	p.Gly483Gly	synonymous	Exon 11 of 15	ENSP00000498630.1
IL31RA	ENST00000359040.10	TSL:1	c.1449T>G	p.Gly483Gly	synonymous	Exon 11 of 16	ENSP00000351935.5
IL31RA	ENST00000490985.5	TSL:1	c.1023T>G	p.Gly341Gly	synonymous	Exon 12 of 16	ENSP00000427533.1

Frequencies

GnomAD3 genomes

AF:

0.131

AC:

19911

AN:

151764

Hom.:

1610

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0543

Gnomad AMI

AF:

0.0989

Gnomad AMR

AF:

0.127

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.00696

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.178

Gnomad OTH

AF:

0.148

GnomAD2 exomes

AF:

0.135

AC:

34054

AN:

251436

AF XY:

0.139

show subpopulations

Gnomad AFR exome

AF:

0.0533

Gnomad AMR exome

AF:

0.0910

Gnomad ASJ exome

AF:

0.167

Gnomad EAS exome

AF:

0.00190

Gnomad FIN exome

AF:

0.191

Gnomad NFE exome

AF:

0.172

Gnomad OTH exome

AF:

0.163

GnomAD4 exome

AF:

0.160

AC:

233619

AN:

1461876

Hom.:

19784

Cov.:

AF XY:

0.159

AC XY:

115645

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.0514

AC:

1721

AN:

33480

American (AMR)

AF:

0.0930

AC:

4158

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

4560

AN:

26134

East Asian (EAS)

AF:

0.00897

AC:

356

AN:

39700

South Asian (SAS)

AF:

0.117

AC:

10095

AN:

86258

European-Finnish (FIN)

AF:

0.191

AC:

10188

AN:

53416

Middle Eastern (MID)

AF:

0.180

AC:

1038

AN:

5768

European-Non Finnish (NFE)

AF:

0.173

AC:

192162

AN:

1112000

Other (OTH)

AF:

0.155

AC:

9341

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

13049

26098

39148

52197

65246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6560

13120

19680

26240

32800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.131

AC:

19913

AN:

151882

Hom.:

1609

Cov.:

AF XY:

0.131

AC XY:

9738

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.0544

AC:

2253

AN:

41410

American (AMR)

AF:

0.127

AC:

1940

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.175

AC:

605

AN:

3466

East Asian (EAS)

AF:

0.00697

AC:

AN:

5162

South Asian (SAS)

AF:

0.105

AC:

506

AN:

4810

European-Finnish (FIN)

AF:

0.192

AC:

2016

AN:

10524

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.178

AC:

12090

AN:

67948

Other (OTH)

AF:

0.146

AC:

306

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

865

1731

2596

3462

4327

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

220

440

660

880

1100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.159

Hom.:

4106

Bravo

AF:

0.121

Asia WGS

AF:

0.0650

AC:

227

AN:

3478

EpiCase

AF:

0.180

EpiControl

AF:

0.175

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Amyloidosis, primary localized cutaneous, 2

Benign:1

May 18, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

IL31RA-related disorder

Benign:1

Nov 19, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

5.6

(source)

DANN

Benign

0.67

PhyloP100

-0.61

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over