Genetic Variant IL31RA:p.Pro43Pro (chr5-55859574-C-G) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_139017.7(IL31RA):c.129C>G(p.Pro43Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P43P) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IL31RA
NM_139017.7 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.288

Publications

0 publications found

Variant links:

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

IL31RA links:

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new If you want to explore the variant's impact on the transcript NM_139017.7, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP7

Synonymous conserved (PhyloP=-0.288 with no splicing effect.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL31RA	NM_139017.7	MANE Select	c.129C>G	p.Pro43Pro	synonymous	Exon 2 of 15	NP_620586.3
IL31RA	NM_001242636.2		c.72C>G	p.Pro24Pro	synonymous	Exon 2 of 15	NP_001229565.1	Q8NI17-12
IL31RA	NM_001242637.2		c.129C>G	p.Pro43Pro	synonymous	Exon 2 of 16	NP_001229566.1	Q8NI17-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL31RA	ENST00000652347.2	MANE Select	c.129C>G	p.Pro43Pro	synonymous	Exon 2 of 15	ENSP00000498630.1	Q8NI17-2
IL31RA	ENST00000359040.10	TSL:1	c.129C>G	p.Pro43Pro	synonymous	Exon 2 of 16	ENSP00000351935.5	Q8NI17-5
IL31RA	ENST00000396836.6	TSL:1	c.129C>G	p.Pro43Pro	synonymous	Exon 2 of 11	ENSP00000380048.2	Q8NI17-8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461252

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727002

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111416

Other (OTH)

AF:

0.00

AC:

AN:

60384

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.64

(source)

DANN

Benign

0.55

PhyloP100

-0.29

PromoterAI

0.062

Neutral

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over