5-55910616-G-T

Variant names:

• chr5-55910616-G-T
• rs161704
• NM_139017.7:c.1586G>T
• IL31RA p.Ser529Ile

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_139017.7(IL31RA):​c.1586G>T​(p.Ser529Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S529N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL31RA NM_139017.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.327
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1586G>T	p.Ser529Ile	missense	Exon 12 of 15	NP_620586.3
	IL31RA	NM_001242636.2		c.1529G>T	p.Ser510Ile	missense	Exon 12 of 15	NP_001229565.1	Q8NI17-12
	IL31RA	NM_001242637.2		c.1586G>T	p.Ser529Ile	missense	Exon 12 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.1586G>T	p.Ser529Ile	missense	Exon 12 of 15	ENSP00000498630.1	Q8NI17-2
	IL31RA	ENST00000359040.10	TSL:1	c.1586G>T	p.Ser529Ile	missense	Exon 12 of 16	ENSP00000351935.5	Q8NI17-5
	IL31RA	ENST00000490985.5	TSL:1	c.1160G>T	p.Ser387Ile	missense	Exon 13 of 16	ENSP00000427533.1	Q8NI17-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Uncertain	1.0
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.45	T
PhyloP100		0.33
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.41
Sift	Benign	0.036	D
Sift4G	Uncertain	0.0040	D
Mutation Taster		=74/26	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs161704;

hg19: chr5-55206444;