rs16884641

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-55916618-T-G
• chr5-55916618-T-A
• chr5-55916618-T-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_139017.7(IL31RA):​c.1819-26T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,602,264 control chromosomes in the GnomAD database, including 56,177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4554 hom., cov: 31)
  • Exomes 𝑓: 0.26 (51623 hom.)
• Consequence: IL31RA NM_139017.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-55916618-T-G is Benign according to our data. Variant chr5-55916618-T-G is described in ClinVar as Benign. ClinVar VariationId is 1300055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL31RA	NM_139017.7	MANE Select	c.1819-26T>G		intron	N/A	NP_620586.3
	IL31RA	NM_001242636.2		c.1762-26T>G		intron	N/A	NP_001229565.1	Q8NI17-12
	IL31RA	NM_001242637.2		c.1819-26T>G		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>G		intron	N/A	ENSP00000498630.1	Q8NI17-2
	IL31RA	ENST00000359040.10	TSL:1	c.1819-26T>G		intron	N/A	ENSP00000351935.5	Q8NI17-5
	IL31RA	ENST00000490985.5	TSL:1	c.1393-26T>G		intron	N/A	ENSP00000427533.1	Q8NI17-6

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33444 AN: 151882 Hom.: 4559 Cov.: 31

Gnomad AFR AF: 0.0645

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.224

GnomAD2 exomes AF: 0.285 AC: 71709 AN: 251254 AF XY: 0.287

Gnomad AFR exome AF: 0.0616

Gnomad AMR exome AF: 0.356

Gnomad ASJ exome AF: 0.339

Gnomad EAS exome AF: 0.493

Gnomad FIN exome AF: 0.300

Gnomad NFE exome AF: 0.250

Gnomad OTH exome AF: 0.291

GnomAD4 exome AF: 0.260 AC: 377663 AN: 1450264 Hom.: 51623 Cov.: 30 AF XY: 0.262 AC XY: 189087 AN XY: 722208

African (AFR) AF: 0.0571 AC: 1899 AN: 33286

American (AMR) AF: 0.345 AC: 15412 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 8860 AN: 26060

East Asian (EAS) AF: 0.442 AC: 17508 AN: 39626

South Asian (SAS) AF: 0.303 AC: 26027 AN: 85992

European-Finnish (FIN) AF: 0.293 AC: 15662 AN: 53378

Middle Eastern (MID) AF: 0.245 AC: 1412 AN: 5752

European-Non Finnish (NFE) AF: 0.250 AC: 274978 AN: 1101458

Other (OTH) AF: 0.265 AC: 15905 AN: 59998

GnomAD4 genome AF: 0.220 AC: 33445 AN: 152000 Hom.: 4554 Cov.: 31 AF XY: 0.229 AC XY: 16982 AN XY: 74278

African (AFR) AF: 0.0646 AC: 2679 AN: 41490

American (AMR) AF: 0.306 AC: 4670 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1128 AN: 3468

East Asian (EAS) AF: 0.477 AC: 2453 AN: 5140

South Asian (SAS) AF: 0.330 AC: 1591 AN: 4814

European-Finnish (FIN) AF: 0.308 AC: 3250 AN: 10558

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 16998 AN: 67956

Other (OTH) AF: 0.224 AC: 473 AN: 2110

Alfa AF: 0.245 Hom.: 12767

Bravo AF: 0.216

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Amyloidosis, primary localized cutaneous, 2 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.2
DANN	Benign	0.60
PhyloP100		0.48
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: rs16884641; hg19: chr5-55212446; COSMIC: COSV61693092;