5-55872429-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_139017.7(IL31RA):c.432A>G(p.Thr144=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,604,496 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (8 hom.)
• Consequence: IL31RA NM_139017.7 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.322

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 5-55872429-A-G is Benign according to our data. Variant chr5-55872429-A-G is described in ClinVar as [Benign]. Clinvar id is 720667.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.322 with no splicing effect.
• BS2: High AC in GnomAd at 214 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL31RA	NM_139017.7	c.432A>G	p.Thr144=	synonymous_variant	4/15	ENST00000652347.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL31RA	ENST00000652347.2	c.432A>G	p.Thr144=	synonymous_variant	4/15		NM_139017.7	A2

Frequencies

GnomAD3 genomes AF: 0.00141 AC: 214 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00187

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00155 AC: 389 AN: 251062 Hom.: 1 AF XY: 0.00163 AC XY: 221 AN XY: 135702

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000868

Gnomad ASJ exome AF: 0.0116

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00188

Gnomad OTH exome AF: 0.00278

GnomAD4 exome AF: 0.00150 AC: 2180 AN: 1452226 Hom.: 8 Cov.: 29 AF XY: 0.00149 AC XY: 1076 AN XY: 723204

Gnomad4 AFR exome AF: 0.000301

Gnomad4 AMR exome AF: 0.00110

Gnomad4 ASJ exome AF: 0.0113

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000209

Gnomad4 FIN exome AF: 0.0000376

Gnomad4 NFE exome AF: 0.00148

Gnomad4 OTH exome AF: 0.00238

GnomAD4 genome AF: 0.00141 AC: 214 AN: 152270 Hom.: 0 Cov.: 32 AF XY: 0.00138 AC XY: 103 AN XY: 74464

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00187

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00213 Hom.: 0

Bravo AF: 0.00153

EpiCase AF: 0.00191

EpiControl AF: 0.00314

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 09, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.5
Dann	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs148785939; hg19: chr5-55168257; COSMIC: COSV51682661;