5-55859516-C-A

Variant names:

• chr5-55859516-C-A
• NM_139017.7:c.71C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139017.7(IL31RA):​c.71C>A​(p.Pro24His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL31RA NM_139017.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.668
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12592056).

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.71C>A	p.Pro24His	missense	Exon 2 of 15	NP_620586.3
	IL31RA	NM_001242636.2		c.14C>A	p.Pro5His	missense	Exon 2 of 15	NP_001229565.1	Q8NI17-12
	IL31RA	NM_001242637.2		c.71C>A	p.Pro24His	missense	Exon 2 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.71C>A	p.Pro24His	missense	Exon 2 of 15	ENSP00000498630.1	Q8NI17-2
	IL31RA	ENST00000359040.10	TSL:1	c.71C>A	p.Pro24His	missense	Exon 2 of 16	ENSP00000351935.5	Q8NI17-5
	IL31RA	ENST00000396836.6	TSL:1	c.71C>A	p.Pro24His	missense	Exon 2 of 11	ENSP00000380048.2	Q8NI17-8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Uncertain	0.98
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.67
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.072
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.014	D
Polyphen		0.0040	B
Vest4		0.19
MutPred		0.64		Loss of sheet (P = 0.0025)
MVP		0.067
MPC		0.31
ClinPred		0.36	T
GERP RS		-3.2
PromoterAI		-0.0024	Neutral
Mutation Taster		=94/6	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

hg19: chr5-55155344;