rs161704

Variant names:

• chr5-55910616-G-A
• rs161704
• NM_139017.7:c.1586G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-55910616-G-A
• chr5-55910616-G-C
• chr5-55910616-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_139017.7(IL31RA):​c.1586G>A​(p.Ser529Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,613,250 control chromosomes in the GnomAD database, including 75,081 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.30 (7183 hom., cov: 32)
  • Exomes 𝑓: 0.30 (67898 hom.)
• Consequence: IL31RA NM_139017.7 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.327
• Publications: 26 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013931394).
• BP6: Variant 5-55910616-G-A is Benign according to our data. Variant chr5-55910616-G-A is described in ClinVar as Benign. ClinVar VariationId is 3060128.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.337 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.1586G>A	p.Ser529Asn	missense	Exon 12 of 15	NP_620586.3
	IL31RA	NM_001242636.2		c.1529G>A	p.Ser510Asn	missense	Exon 12 of 15	NP_001229565.1	Q8NI17-12
	IL31RA	NM_001242637.2		c.1586G>A	p.Ser529Asn	missense	Exon 12 of 16	NP_001229566.1	Q8NI17-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL31RA	ENST00000652347.2	MANE Select	c.1586G>A	p.Ser529Asn	missense	Exon 12 of 15	ENSP00000498630.1	Q8NI17-2
	IL31RA	ENST00000359040.10	TSL:1	c.1586G>A	p.Ser529Asn	missense	Exon 12 of 16	ENSP00000351935.5	Q8NI17-5
	IL31RA	ENST00000490985.5	TSL:1	c.1160G>A	p.Ser387Asn	missense	Exon 13 of 16	ENSP00000427533.1	Q8NI17-6

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46112 AN: 151972 Hom.: 7185 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.281

GnomAD2 exomes AF: 0.293 AC: 73677 AN: 251458 AF XY: 0.297

Gnomad AFR exome AF: 0.343

Gnomad AMR exome AF: 0.191

Gnomad ASJ exome AF: 0.217

Gnomad EAS exome AF: 0.327

Gnomad FIN exome AF: 0.282

Gnomad NFE exome AF: 0.303

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.302 AC: 441483 AN: 1461160 Hom.: 67898 Cov.: 35 AF XY: 0.304 AC XY: 220815 AN XY: 726980

African (AFR) AF: 0.341 AC: 11408 AN: 33470

American (AMR) AF: 0.198 AC: 8874 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 5618 AN: 26130

East Asian (EAS) AF: 0.374 AC: 14853 AN: 39696

South Asian (SAS) AF: 0.362 AC: 31207 AN: 86242

European-Finnish (FIN) AF: 0.287 AC: 15356 AN: 53414

Middle Eastern (MID) AF: 0.223 AC: 1288 AN: 5768

European-Non Finnish (NFE) AF: 0.302 AC: 335510 AN: 1111362

Other (OTH) AF: 0.288 AC: 17369 AN: 60360

GnomAD4 genome AF: 0.303 AC: 46137 AN: 152090 Hom.: 7183 Cov.: 32 AF XY: 0.300 AC XY: 22322 AN XY: 74358

African (AFR) AF: 0.342 AC: 14175 AN: 41456

American (AMR) AF: 0.229 AC: 3499 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 724 AN: 3470

East Asian (EAS) AF: 0.335 AC: 1734 AN: 5174

South Asian (SAS) AF: 0.345 AC: 1667 AN: 4826

European-Finnish (FIN) AF: 0.278 AC: 2941 AN: 10582

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20274 AN: 67984

Other (OTH) AF: 0.286 AC: 603 AN: 2112

Alfa AF: 0.298 Hom.: 26960

Bravo AF: 0.299

TwinsUK AF: 0.316 AC: 1170

ALSPAC AF: 0.309 AC: 1190

ESP6500AA AF: 0.343 AC: 1511

ESP6500EA AF: 0.291 AC: 2503

ExAC AF: 0.301 AC: 36588

Asia WGS AF: 0.345 AC: 1200 AN: 3478

EpiCase AF: 0.286

EpiControl AF: 0.289

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	IL31RA-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.25
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.034
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.62	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-0.99	T
PhyloP100		0.33
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	0.24	T
Polyphen		0.14	B
Vest4		0.050
MPC		0.11
ClinPred		0.0049	T
GERP RS		3.3
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs161704; hg19: chr5-55206444; COSMIC: COSV51679047; COSMIC: COSV51679047;