chr5-55913344-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_139017.7(IL31RA):​c.1643-133G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000538 in 557,150 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000054 (0 hom.)
• Consequence: IL31RA NM_139017.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.925
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

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>T		intron	N/A	NP_620586.3
	IL31RA	NM_001242636.2		c.1586-133G>T		intron	N/A	NP_001229565.1
	IL31RA	NM_001242637.2		c.1643-133G>T		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>T		intron	N/A	ENSP00000498630.1
	IL31RA	ENST00000359040.10	TSL:1	c.1643-133G>T		intron	N/A	ENSP00000351935.5
	IL31RA	ENST00000490985.5	TSL:1	c.1217-133G>T		intron	N/A	ENSP00000427533.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000538 AC: 3 AN: 557150 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 299714

African (AFR) AF: 0.00 AC: 0 AN: 14828

American (AMR) AF: 0.00 AC: 0 AN: 29660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18700

East Asian (EAS) AF: 0.00 AC: 0 AN: 31938

South Asian (SAS) AF: 0.00 AC: 0 AN: 57148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40834

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2424

European-Non Finnish (NFE) AF: 0.00000905 AC: 3 AN: 331622

Other (OTH) AF: 0.00 AC: 0 AN: 29996

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.85
DANN	Benign	0.43
PhyloP100		-0.93

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;