Genetic Variant IL31RA:c.455-125A>C (chr5-55882919-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_139017.7(IL31RA):c.455-125A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 858,518 control chromosomes in the GnomAD database, including 27,404 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 4117 hom., cov: 31)

Exomes 𝑓: 0.25 ( 23287 hom. )

Consequence

IL31RA
NM_139017.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.199

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL31RA	NM_139017.7 link	c.455-125A>C		intron_variant	Intron 4 of 14	ENST00000652347.2	NP_620586.3	Q8NI17-2B4DNJ2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL31RA	ENST00000652347.2 link	c.455-125A>C		intron_variant	Intron 4 of 14		NM_139017.7	ENSP00000498630.1		Q8NI17-2

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

32969

AN:

151896

Hom.:

4119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.257

Gnomad AMR

AF:

0.304

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.407

Gnomad SAS

AF:

0.274

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.236

Gnomad OTH

AF:

0.213

GnomAD4 exome

AF:

0.250

AC:

176522

AN:

706504

Hom.:

23287

AF XY:

0.249

AC XY:

93382

AN XY:

375148

show subpopulations

African (AFR)

AF:

0.102

AC:

1902

AN:

18736

American (AMR)

AF:

0.335

AC:

12291

AN:

36658

Ashkenazi Jewish (ASJ)

AF:

0.243

AC:

4989

AN:

20508

East Asian (EAS)

AF:

0.397

AC:

14009

AN:

35268

South Asian (SAS)

AF:

0.251

AC:

16664

AN:

66290

European-Finnish (FIN)

AF:

0.278

AC:

11695

AN:

42092

Middle Eastern (MID)

AF:

0.236

AC:

626

AN:

2654

European-Non Finnish (NFE)

AF:

0.236

AC:

105852

AN:

449152

Other (OTH)

AF:

0.242

AC:

8494

AN:

35146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

6704

13409

20113

26818

33522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2000

4000

6000

8000

10000

<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:

0.217

AC:

32973

AN:

152014

Hom.:

4117

Cov.:

AF XY:

0.224

AC XY:

16614

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.101

AC:

4188

AN:

41470

American (AMR)

AF:

0.303

AC:

4630

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.234

AC:

811

AN:

3470

East Asian (EAS)

AF:

0.406

AC:

2099

AN:

5168

South Asian (SAS)

AF:

0.275

AC:

1326

AN:

4816

European-Finnish (FIN)

AF:

0.296

AC:

3122

AN:

10550

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.236

AC:

16052

AN:

67956

Other (OTH)

AF:

0.214

AC:

451

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1277

2554

3830

5107

6384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

358

716

1074

1432

1790

<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:

0.224

Hom.:

8481

Bravo

AF:

0.215

Asia WGS

AF:

0.327

AC:

1137

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over