rs9292101

Variant names:

• chr5-55854376-G-T
• rs9292101
• NM_139017.7:c.63+2743G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139017.7(IL31RA):​c.63+2743G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 152,178 control chromosomes in the GnomAD database, including 43,909 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.75 (43909 hom., cov: 33)
• Consequence: IL31RA NM_139017.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 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.63+2743G>T		intron	N/A	NP_620586.3
	IL31RA	NM_001242636.2		c.6+809G>T		intron	N/A	NP_001229565.1	Q8NI17-12
	IL31RA	NM_001242637.2		c.63+2743G>T		intron	N/A	NP_001229566.1	Q8NI17-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL31RA	ENST00000652347.2	MANE Select	c.63+2743G>T		intron	N/A	ENSP00000498630.1	Q8NI17-2
	IL31RA	ENST00000359040.10	TSL:1	c.63+2743G>T		intron	N/A	ENSP00000351935.5	Q8NI17-5
	IL31RA	ENST00000490985.5	TSL:1	c.-508+809G>T		intron	N/A	ENSP00000427533.1	Q8NI17-6

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114629 AN: 152060 Hom.: 43873 Cov.: 33

Gnomad AFR AF: 0.830

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.744

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.754 AC: 114728 AN: 152178 Hom.: 43909 Cov.: 33 AF XY: 0.752 AC XY: 55955 AN XY: 74390

African (AFR) AF: 0.830 AC: 34460 AN: 41530

American (AMR) AF: 0.590 AC: 9006 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2704 AN: 3472

East Asian (EAS) AF: 0.477 AC: 2474 AN: 5186

South Asian (SAS) AF: 0.769 AC: 3705 AN: 4820

European-Finnish (FIN) AF: 0.799 AC: 8452 AN: 10578

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.757 AC: 51449 AN: 68006

Other (OTH) AF: 0.746 AC: 1572 AN: 2106

Alfa AF: 0.773 Hom.: 5913

Bravo AF: 0.734

Asia WGS AF: 0.660 AC: 2296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.4
DANN	Benign	0.60
PhyloP100		0.024
Mutation Taster		=100/0	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: rs9292101; hg19: chr5-55150204; COSMIC: COSV51680409;