chr5-55913344-G-A

Variant names:

• chr5-55913344-G-A
• rs12153724
• NM_139017.7:c.1643-133G>A

Variant summary

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

The NM_139017.7(IL31RA):​c.1643-133G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 708,604 control chromosomes in the GnomAD database, including 27,446 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 0.23 (4810 hom., cov: 32)
  • Exomes 𝑓: 0.28 (22636 hom.)
• Consequence: IL31RA NM_139017.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.925
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL31RA	NM_139017.7	MANE Select	c.1643-133G>A		intron	N/A	NP_620586.3
	IL31RA	NM_001242636.2		c.1586-133G>A		intron	N/A	NP_001229565.1
	IL31RA	NM_001242637.2		c.1643-133G>A		intron	N/A	NP_001229566.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL31RA	ENST00000652347.2	MANE Select	c.1643-133G>A		intron	N/A	ENSP00000498630.1
	IL31RA	ENST00000359040.10	TSL:1	c.1643-133G>A		intron	N/A	ENSP00000351935.5
	IL31RA	ENST00000490985.5	TSL:1	c.1217-133G>A		intron	N/A	ENSP00000427533.1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 35008 AN: 151936 Hom.: 4813 Cov.: 32

Gnomad AFR AF: 0.0856

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.232

GnomAD4 exome AF: 0.277 AC: 154222 AN: 556550 Hom.: 22636 AF XY: 0.278 AC XY: 83261 AN XY: 299378

African (AFR) AF: 0.0817 AC: 1211 AN: 14824

American (AMR) AF: 0.339 AC: 10019 AN: 29598

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 6280 AN: 18674

East Asian (EAS) AF: 0.430 AC: 13731 AN: 31912

South Asian (SAS) AF: 0.299 AC: 17092 AN: 57102

European-Finnish (FIN) AF: 0.295 AC: 12011 AN: 40758

Middle Eastern (MID) AF: 0.256 AC: 619 AN: 2418

European-Non Finnish (NFE) AF: 0.257 AC: 85114 AN: 331284

Other (OTH) AF: 0.272 AC: 8145 AN: 29980

GnomAD4 genome AF: 0.230 AC: 35015 AN: 152054 Hom.: 4810 Cov.: 32 AF XY: 0.238 AC XY: 17693 AN XY: 74322

African (AFR) AF: 0.0857 AC: 3559 AN: 41536

American (AMR) AF: 0.312 AC: 4767 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1124 AN: 3466

East Asian (EAS) AF: 0.476 AC: 2449 AN: 5144

South Asian (SAS) AF: 0.332 AC: 1598 AN: 4808

European-Finnish (FIN) AF: 0.311 AC: 3279 AN: 10548

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17538 AN: 67948

Other (OTH) AF: 0.233 AC: 491 AN: 2110

Alfa AF: 0.0978 Hom.: 175

Bravo AF: 0.226

Asia WGS AF: 0.343 AC: 1192 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	0.96
DANN	Benign	0.38
PhyloP100		-0.93
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: rs12153724; hg19: chr5-55209172; COSMIC: COSV51682300; COSMIC: COSV51682300;