5-55916618-T-A

Variant names:

• chr5-55916618-T-A
• rs16884641
• NM_139017.7:c.1819-26T>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_139017.7(IL31RA):​c.1819-26T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0057 in 1,603,294 control chromosomes in the GnomAD database, including 36 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 0.0038 (3 hom., cov: 31)
  • Exomes 𝑓: 0.0059 (33 hom.)
• Consequence: IL31RA NM_139017.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.476
• Publications: 7 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS2: High AC in GnomAd4 at 579 AD,Unknown gene.

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.1819-26T>A		intron	N/A	NP_620586.3
	IL31RA	NM_001242636.2		c.1762-26T>A		intron	N/A	NP_001229565.1	Q8NI17-12
	IL31RA	NM_001242637.2		c.1819-26T>A		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.1819-26T>A		intron	N/A	ENSP00000498630.1	Q8NI17-2
	IL31RA	ENST00000359040.10	TSL:1	c.1819-26T>A		intron	N/A	ENSP00000351935.5	Q8NI17-5
	IL31RA	ENST00000490985.5	TSL:1	c.1393-26T>A		intron	N/A	ENSP00000427533.1	Q8NI17-6

Frequencies

GnomAD3 genomes AF: 0.00381 AC: 579 AN: 151942 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.000942

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00331

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00660

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00347 AC: 872 AN: 251254 AF XY: 0.00370

Gnomad AFR exome AF: 0.000985

Gnomad AMR exome AF: 0.00254

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00356

Gnomad NFE exome AF: 0.00578

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00590 AC: 8562 AN: 1451234 Hom.: 33 Cov.: 30 AF XY: 0.00582 AC XY: 4206 AN XY: 722674

African (AFR) AF: 0.000931 AC: 31 AN: 33286

American (AMR) AF: 0.00271 AC: 121 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.000686 AC: 59 AN: 86026

European-Finnish (FIN) AF: 0.00427 AC: 228 AN: 53396

Middle Eastern (MID) AF: 0.000348 AC: 2 AN: 5752

European-Non Finnish (NFE) AF: 0.00707 AC: 7793 AN: 1102328

Other (OTH) AF: 0.00541 AC: 325 AN: 60020

GnomAD4 genome AF: 0.00381 AC: 579 AN: 152060 Hom.: 3 Cov.: 31 AF XY: 0.00346 AC XY: 257 AN XY: 74322

African (AFR) AF: 0.000940 AC: 39 AN: 41502

American (AMR) AF: 0.00301 AC: 46 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4818

European-Finnish (FIN) AF: 0.00331 AC: 35 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00661 AC: 449 AN: 67972

Other (OTH) AF: 0.00332 AC: 7 AN: 2110

Alfa AF: 0.000148 Hom.: 12767

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.6
DANN	Benign	0.62
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism

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: rs16884641; hg19: chr5-55212446;