5-55859576-C-T

Variant names:

• chr5-55859576-C-T
• rs140536651
• NM_139017.7:c.131C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_139017.7(IL31RA):​c.131C>T​(p.Ser44Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000691 in 1,612,090 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00035 (3 hom.)
• Consequence: IL31RA NM_139017.7 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.83
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0044793785).
• BP6: Variant 5-55859576-C-T is Benign according to our data. Variant chr5-55859576-C-T is described in ClinVar as Benign. ClinVar VariationId is 785123.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 600 Unknown,AD 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.131C>T	p.Ser44Leu	missense	Exon 2 of 15	NP_620586.3
	IL31RA	NM_001242636.2		c.74C>T	p.Ser25Leu	missense	Exon 2 of 15	NP_001229565.1	Q8NI17-12
	IL31RA	NM_001242637.2		c.131C>T	p.Ser44Leu	missense	Exon 2 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.131C>T	p.Ser44Leu	missense	Exon 2 of 15	ENSP00000498630.1	Q8NI17-2
	IL31RA	ENST00000359040.10	TSL:1	c.131C>T	p.Ser44Leu	missense	Exon 2 of 16	ENSP00000351935.5	Q8NI17-5
	IL31RA	ENST00000396836.6	TSL:1	c.131C>T	p.Ser44Leu	missense	Exon 2 of 11	ENSP00000380048.2	Q8NI17-8

Frequencies

GnomAD3 genomes AF: 0.00393 AC: 598 AN: 152180 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0139

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000994 AC: 250 AN: 251408 AF XY: 0.000699

Gnomad AFR exome AF: 0.0143

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000352 AC: 514 AN: 1459792 Hom.: 3 Cov.: 31 AF XY: 0.000275 AC XY: 200 AN XY: 726190

African (AFR) AF: 0.0134 AC: 447 AN: 33432

American (AMR) AF: 0.000493 AC: 22 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1110284

Other (OTH) AF: 0.000630 AC: 38 AN: 60332

GnomAD4 genome AF: 0.00394 AC: 600 AN: 152298 Hom.: 5 Cov.: 32 AF XY: 0.00380 AC XY: 283 AN XY: 74482

African (AFR) AF: 0.0139 AC: 576 AN: 41554

American (AMR) AF: 0.00118 AC: 18 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00166 Hom.: 3

Bravo AF: 0.00433

ESP6500AA AF: 0.0186 AC: 82

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00138 AC: 168

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.4
DANN	Benign	0.12
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.0045	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.8
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.99	N
REVEL	Benign	0.093
Sift	Benign	0.41	T
Sift4G	Benign	0.68	T
Polyphen		0.0	B
Vest4		0.12
MVP		0.055
MPC		0.099
ClinPred		0.0046	T
GERP RS		3.0
PromoterAI		-0.028	Neutral
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs140536651; hg19: chr5-55155404;