NM_139017.7:c.1252+435T>C

Variant names:

• chr5-55906723-T-C
• rs324454
• NM_139017.7:c.1252+435T>C

Variant summary

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

The NM_139017.7(IL31RA):​c.1252+435T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 152,114 control chromosomes in the GnomAD database, including 32,136 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 0.64 (32136 hom., cov: 32)
• Consequence: IL31RA NM_139017.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL31RA	NM_139017.7	c.1252+435T>C		intron_variant	Intron 9 of 14	ENST00000652347.2	NP_620586.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL31RA	ENST00000652347.2	c.1252+435T>C		intron_variant	Intron 9 of 14		NM_139017.7	ENSP00000498630.1

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97471 AN: 151996 Hom.: 32111 Cov.: 32

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.641 AC: 97553 AN: 152114 Hom.: 32136 Cov.: 32 AF XY: 0.642 AC XY: 47758 AN XY: 74372

African (AFR) AF: 0.788 AC: 32684 AN: 41464

American (AMR) AF: 0.588 AC: 8989 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1922 AN: 3470

East Asian (EAS) AF: 0.815 AC: 4227 AN: 5188

South Asian (SAS) AF: 0.679 AC: 3274 AN: 4822

European-Finnish (FIN) AF: 0.596 AC: 6301 AN: 10570

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38140 AN: 67990

Other (OTH) AF: 0.604 AC: 1275 AN: 2110

Alfa AF: 0.590 Hom.: 80159

Bravo AF: 0.648

Asia WGS AF: 0.713 AC: 2480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.22
DANN	Benign	0.54
PhyloP100		-2.7
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: rs324454; hg19: chr5-55202551;