Variant 12-122173924-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001014336.2(IL31):c.85G>A(p.Val29Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000186 in 1,613,998 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 6 hom. )

Consequence

IL31
NM_001014336.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.07

Variant links:

Genes affected

IL31 (HGNC:19372): (interleukin 31) IL31, which is made principally by activated Th2-type T cells, interacts with a heterodimeric receptor consisting of IL31RA (MIM 609510) and OSMR (MIM 601743) that is constitutively expressed on epithelial cells and keratinocytes. IL31 may be involved in the promotion of allergic skin disorders and in regulating other allergic diseases, such as asthma (Dillon et al., 2004 [PubMed 15184896]).[supplied by OMIM, Mar 2008]

IL31 links:

LRRC43 (HGNC:28562): (leucine rich repeat containing 43)

LRRC43 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.030079693).

BP6

Variant 12-122173924-C-T is Benign according to our data. Variant chr12-122173924-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3109383.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL31	NM_001014336.2 linkuse as main transcript	c.85G>A	p.Val29Ile	missense_variant	2/3	ENST00000377035.2	NP_001014358.1	Q6EBC2
LRRC43	NM_152759.5 linkuse as main transcript	c.-406+6142C>T		intron_variant			NP_689972.3	Q8N309-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL31	ENST00000377035.2 linkuse as main transcript	c.85G>A	p.Val29Ile	missense_variant	2/3	1	NM_001014336.2	ENSP00000366234.1		Q6EBC2
LRRC43	ENST00000537729.5 linkuse as main transcript	c.-406+6142C>T		intron_variant		5		ENSP00000438751.1		F5H0N3

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000676

AC:

AN:

251436

Hom.:

AF XY:

0.0000662

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000201

AC:

294

AN:

1461866

Hom.:

Cov.:

AF XY:

0.000199

AC XY:

145

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000179

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000185

Hom.:

Bravo

AF:

0.0000945

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.0030

DANN

Benign

0.86

DEOGEN2

Benign

0.030

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.00038

LIST_S2

Benign

0.30

M_CAP

Benign

0.0011

MetaRNN

Benign

0.030

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

PrimateAI

Benign

0.24

PROVEAN

Benign

0.36

REVEL

Benign

0.010

Sift

Benign

0.73

Sift4G

Benign

0.69

Polyphen

0.010

Vest4

0.039

MVP

0.030

MPC

0.36

ClinPred

0.034

GERP RS

-9.0

Varity_R

0.016

gMVP

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over