chr5-55889536-C-T

Variant names:

• chr5-55889536-C-T
• rs6861890
• NM_139017.7:c.607-434C>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.607-434C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,142 control chromosomes in the GnomAD database, including 16,218 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 0.46 (16218 hom., cov: 33)
• Consequence: IL31RA NM_139017.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225
• 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: 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.522 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.607-434C>T		intron	N/A	NP_620586.3
	IL31RA	NM_001242636.2		c.550-434C>T		intron	N/A	NP_001229565.1
	IL31RA	NM_001242637.2		c.607-434C>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.607-434C>T		intron	N/A	ENSP00000498630.1
	IL31RA	ENST00000359040.10	TSL:1	c.607-434C>T		intron	N/A	ENSP00000351935.5
	IL31RA	ENST00000490985.5	TSL:1	c.181-434C>T		intron	N/A	ENSP00000427533.1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69419 AN: 152024 Hom.: 16218 Cov.: 33

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.456 AC: 69445 AN: 152142 Hom.: 16218 Cov.: 33 AF XY: 0.454 AC XY: 33804 AN XY: 74382

African (AFR) AF: 0.403 AC: 16704 AN: 41478

American (AMR) AF: 0.363 AC: 5555 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1533 AN: 3470

East Asian (EAS) AF: 0.357 AC: 1848 AN: 5176

South Asian (SAS) AF: 0.540 AC: 2604 AN: 4826

European-Finnish (FIN) AF: 0.480 AC: 5078 AN: 10584

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.508 AC: 34513 AN: 68002

Other (OTH) AF: 0.461 AC: 974 AN: 2112

Alfa AF: 0.474 Hom.: 3168

Bravo AF: 0.438

Asia WGS AF: 0.447 AC: 1553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.89
DANN	Benign	0.58
PhyloP100		-0.23
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: rs6861890; hg19: chr5-55185364;