rs9632389

Variant names:

• chr5-55908359-T-G
• rs9632389
• NM_139017.7:c.1449T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-55908359-T-G
• chr5-55908359-T-A
• chr5-55908359-T-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.612
• Publications: 16 publications found

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: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	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	Q8NI17-12
	IL31RA	NM_001242637.2		c.1449T>G	p.Gly483Gly	synonymous	Exon 11 of 16	NP_001229566.1	Q8NI17-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL31RA	ENST00000652347.2	MANE Select	c.1449T>G	p.Gly483Gly	synonymous	Exon 11 of 15	ENSP00000498630.1	Q8NI17-2
	IL31RA	ENST00000359040.10	TSL:1	c.1449T>G	p.Gly483Gly	synonymous	Exon 11 of 16	ENSP00000351935.5	Q8NI17-5
	IL31RA	ENST00000490985.5	TSL:1	c.1023T>G	p.Gly341Gly	synonymous	Exon 12 of 16	ENSP00000427533.1	Q8NI17-6

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19911 AN: 151764 Hom.: 1610 Cov.: 32

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

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.: 32 AF XY: 0.159 AC XY: 115645 AN XY: 727240

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

GnomAD4 genome AF: 0.131 AC: 19913 AN: 151882 Hom.: 1609 Cov.: 32 AF XY: 0.131 AC XY: 9738 AN XY: 74212

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: 36 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: 71 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12090 AN: 67948

Other (OTH) AF: 0.146 AC: 306 AN: 2102

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Amyloidosis, primary localized cutaneous, 2 (1)
-	-	1	IL31RA-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.6
DANN	Benign	0.67
PhyloP100		-0.61
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9632389; hg19: chr5-55204187; COSMIC: COSV51681426;