rs1009639

Variant names:

• chr5-55859574-C-T
• rs1009639
• NM_139017.7:c.129C>T

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.129C>T​(p.Pro43Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 1,612,148 control chromosomes in the GnomAD database, including 418,680 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (37265 hom., cov: 32)
  • Exomes 𝑓: 0.72 (381415 hom.)
• Consequence: IL31RA NM_139017.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.288
• Publications: 20 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: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-55859574-C-T is Benign according to our data. Variant chr5-55859574-C-T is described in ClinVar as Benign. ClinVar VariationId is 1300053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.288 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.744 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.129C>T	p.Pro43Pro	synonymous	Exon 2 of 15	NP_620586.3
	IL31RA	NM_001242636.2		c.72C>T	p.Pro24Pro	synonymous	Exon 2 of 15	NP_001229565.1
	IL31RA	NM_001242637.2		c.129C>T	p.Pro43Pro	synonymous	Exon 2 of 16	NP_001229566.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL31RA	ENST00000652347.2	MANE Select	c.129C>T	p.Pro43Pro	synonymous	Exon 2 of 15	ENSP00000498630.1
	IL31RA	ENST00000359040.10	TSL:1	c.129C>T	p.Pro43Pro	synonymous	Exon 2 of 16	ENSP00000351935.5
	IL31RA	ENST00000396836.6	TSL:1	c.129C>T	p.Pro43Pro	synonymous	Exon 2 of 11	ENSP00000380048.2

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105685 AN: 151948 Hom.: 37245 Cov.: 32

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.694

GnomAD2 exomes AF: 0.676 AC: 170006 AN: 251414 AF XY: 0.692

Gnomad AFR exome AF: 0.660

Gnomad AMR exome AF: 0.424

Gnomad ASJ exome AF: 0.738

Gnomad EAS exome AF: 0.465

Gnomad FIN exome AF: 0.769

Gnomad NFE exome AF: 0.736

Gnomad OTH exome AF: 0.703

GnomAD4 exome AF: 0.719 AC: 1049850 AN: 1460080 Hom.: 381415 Cov.: 38 AF XY: 0.723 AC XY: 524905 AN XY: 726504

African (AFR) AF: 0.665 AC: 22239 AN: 33432

American (AMR) AF: 0.439 AC: 19621 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 19477 AN: 26128

East Asian (EAS) AF: 0.495 AC: 19630 AN: 39694

South Asian (SAS) AF: 0.781 AC: 67371 AN: 86214

European-Finnish (FIN) AF: 0.768 AC: 41027 AN: 53418

Middle Eastern (MID) AF: 0.762 AC: 4390 AN: 5762

European-Non Finnish (NFE) AF: 0.732 AC: 812771 AN: 1110364

Other (OTH) AF: 0.718 AC: 43324 AN: 60352

GnomAD4 genome AF: 0.695 AC: 105761 AN: 152068 Hom.: 37265 Cov.: 32 AF XY: 0.696 AC XY: 51752 AN XY: 74340

African (AFR) AF: 0.671 AC: 27830 AN: 41486

American (AMR) AF: 0.557 AC: 8512 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2554 AN: 3472

East Asian (EAS) AF: 0.475 AC: 2451 AN: 5158

South Asian (SAS) AF: 0.765 AC: 3686 AN: 4820

European-Finnish (FIN) AF: 0.782 AC: 8277 AN: 10590

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.737 AC: 50097 AN: 67958

Other (OTH) AF: 0.697 AC: 1470 AN: 2110

Alfa AF: 0.711 Hom.: 61602

Bravo AF: 0.668

Asia WGS AF: 0.646 AC: 2249 AN: 3478

EpiCase AF: 0.739

EpiControl AF: 0.737

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.85
DANN	Benign	0.48
PhyloP100		-0.29
PromoterAI		0.027	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1009639; hg19: chr5-55155402; COSMIC: COSV51681840;