5-55883224-A-T

Variant names:

• chr5-55883224-A-T
• rs10940491
• NM_139017.7:c.606+29A>T

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.606+29A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 1,562,168 control chromosomes in the GnomAD database, including 267,863 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (31924 hom., cov: 32)
  • Exomes 𝑓: 0.57 (235939 hom.)
• Consequence: IL31RA NM_139017.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0240
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 5-55883224-A-T is Benign according to our data. Variant chr5-55883224-A-T is described in ClinVar as [Benign]. Clinvar id is 1300054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL31RA	NM_139017.7	c.606+29A>T		intron_variant	Intron 5 of 14	ENST00000652347.2	NP_620586.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL31RA	ENST00000652347.2	c.606+29A>T		intron_variant	Intron 5 of 14		NM_139017.7	ENSP00000498630.1

Frequencies

GnomAD3 genomes AF: 0.633 AC: 95929 AN: 151656 Hom.: 31879 Cov.: 32

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.606

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.620

GnomAD2 exomes AF: 0.551 AC: 137985 AN: 250244 AF XY: 0.558

Gnomad AFR exome AF: 0.848

Gnomad AMR exome AF: 0.339

Gnomad ASJ exome AF: 0.564

Gnomad EAS exome AF: 0.375

Gnomad FIN exome AF: 0.554

Gnomad NFE exome AF: 0.576

Gnomad OTH exome AF: 0.551

GnomAD4 exome AF: 0.574 AC: 809025 AN: 1410394 Hom.: 235939 Cov.: 24 AF XY: 0.576 AC XY: 406227 AN XY: 704874

African (AFR) AF: 0.852 AC: 27419 AN: 32200

American (AMR) AF: 0.355 AC: 15816 AN: 44530

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 14811 AN: 25816

East Asian (EAS) AF: 0.426 AC: 16820 AN: 39474

South Asian (SAS) AF: 0.643 AC: 54822 AN: 85210

European-Finnish (FIN) AF: 0.557 AC: 29657 AN: 53278

Middle Eastern (MID) AF: 0.596 AC: 3336 AN: 5600

European-Non Finnish (NFE) AF: 0.574 AC: 612214 AN: 1065786

Other (OTH) AF: 0.583 AC: 34130 AN: 58500

GnomAD4 genome AF: 0.633 AC: 96037 AN: 151774 Hom.: 31924 Cov.: 32 AF XY: 0.627 AC XY: 46521 AN XY: 74192

African (AFR) AF: 0.845 AC: 34980 AN: 41418

American (AMR) AF: 0.459 AC: 6969 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2028 AN: 3470

East Asian (EAS) AF: 0.388 AC: 1999 AN: 5158

South Asian (SAS) AF: 0.623 AC: 3002 AN: 4820

European-Finnish (FIN) AF: 0.553 AC: 5836 AN: 10546

Middle Eastern (MID) AF: 0.622 AC: 179 AN: 288

European-Non Finnish (NFE) AF: 0.577 AC: 39188 AN: 67868

Other (OTH) AF: 0.621 AC: 1306 AN: 2104

Alfa AF: 0.607 Hom.: 5265

Bravo AF: 0.628

Asia WGS AF: 0.539 AC: 1874 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Amyloidosis, primary localized cutaneous, 2 Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.43
PhyloP100		-0.024
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: rs10940491; hg19: chr5-55179052; COSMIC: COSV51682159;