ENST00000490985.5:c.-520C>T

Variant names:

• chr5-55853555-C-T
• rs190185736
• ENST00000490985.5:c.-520C>T

Variant summary

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

The ENST00000490985.5(IL31RA):​c.-520C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00646 in 1,550,846 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0046 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0067 (42 hom.)
• Consequence: IL31RA ENST00000490985.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.372
• Publications: 0 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 (BayesDel_noAF=-0.85).
• BP6: Variant 5-55853555-C-T is Benign according to our data. Variant chr5-55853555-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2655465.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 695 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000490985.5. 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.63+1922C>T		intron	N/A	NP_620586.3
	IL31RA	NM_001242636.2		c.-7C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	NP_001229565.1	Q8NI17-12
	IL31RA	NM_001242638.2		c.-7C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 18	NP_001229567.1	Q8NI17-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL31RA	ENST00000490985.5	TSL:1	c.-520C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 16	ENSP00000427533.1	Q8NI17-6
	IL31RA	ENST00000490985.5	TSL:1	c.-520C>T		5_prime_UTR	Exon 1 of 16	ENSP00000427533.1	Q8NI17-6
	IL31RA	ENST00000652347.2	MANE Select	c.63+1922C>T		intron	N/A	ENSP00000498630.1	Q8NI17-2

Frequencies

GnomAD3 genomes AF: 0.00457 AC: 695 AN: 152214 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00508

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00835

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00419 AC: 633 AN: 151102 AF XY: 0.00422

Gnomad AFR exome AF: 0.000834

Gnomad AMR exome AF: 0.000487

Gnomad ASJ exome AF: 0.00166

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00787

Gnomad NFE exome AF: 0.00800

Gnomad OTH exome AF: 0.00295

GnomAD4 exome AF: 0.00666 AC: 9318 AN: 1398514 Hom.: 42 Cov.: 31 AF XY: 0.00645 AC XY: 4450 AN XY: 689736

African (AFR) AF: 0.000855 AC: 27 AN: 31594

American (AMR) AF: 0.000532 AC: 19 AN: 35706

Ashkenazi Jewish (ASJ) AF: 0.00155 AC: 39 AN: 25174

East Asian (EAS) AF: 0.00 AC: 0 AN: 35732

South Asian (SAS) AF: 0.000265 AC: 21 AN: 79220

European-Finnish (FIN) AF: 0.00787 AC: 381 AN: 48402

Middle Eastern (MID) AF: 0.000351 AC: 2 AN: 5700

European-Non Finnish (NFE) AF: 0.00795 AC: 8577 AN: 1078836

Other (OTH) AF: 0.00433 AC: 252 AN: 58150

GnomAD4 genome AF: 0.00456 AC: 695 AN: 152332 Hom.: 1 Cov.: 33 AF XY: 0.00415 AC XY: 309 AN XY: 74492

African (AFR) AF: 0.00115 AC: 48 AN: 41582

American (AMR) AF: 0.000719 AC: 11 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3468

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

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00508 AC: 54 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00835 AC: 568 AN: 68038

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00664 Hom.: 2

Bravo AF: 0.00405

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.7
DANN	Benign	0.57
PhyloP100		0.37
PromoterAI		-0.035	Neutral
Mutation Taster		=300/0	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: rs190185736; hg19: chr5-55149383;