NM_139017.7:c.1586G>C

Variant names:

• chr5-55910616-G-C
• rs161704
• NM_139017.7:c.1586G>C

Variant summary

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

The NM_139017.7(IL31RA):​c.1586G>C​(p.Ser529Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/18 in silico tools predict a benign outcome for this variant. 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: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL31RA	NM_139017.7	c.1586G>C	p.Ser529Thr	missense_variant	Exon 12 of 15	ENST00000652347.2	NP_620586.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL31RA	ENST00000652347.2	c.1586G>C	p.Ser529Thr	missense_variant	Exon 12 of 15		NM_139017.7	ENSP00000498630.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.70	.;T;T;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.43	T;T;T;T;T;T
MetaSVM	Benign	-0.69	T
PhyloP100		0.33
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.5	N;N;N;N;.;N
REVEL	Benign	0.25
Sift	Benign	0.34	T;T;T;T;.;T
Sift4G	Uncertain	0.044	D;D;D;D;D;D
Polyphen		0.93	P;P;P;P;.;.
Vest4		0.33
MVP		0.33
MPC		0.22
ClinPred		0.73	D
GERP RS		3.3
Mutation Taster		=91/9	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

Other links and lift over

dbSNP: rs161704; hg19: chr5-55206444;