Variant 12-122172724-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001014336.2(IL31):c.183C>G(p.Gly61Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,609,362 control chromosomes in the GnomAD database, including 21,681 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.14 ( 1780 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19901 hom. )

Consequence

IL31
NM_001014336.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.28

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 12-122172724-G-C is Benign according to our data. Variant chr12-122172724-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3109379.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.28 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL31	NM_001014336.2 linkuse as main transcript	c.183C>G	p.Gly61Gly	synonymous_variant	3/3	ENST00000377035.2	NP_001014358.1	Q6EBC2
LRRC43	NM_152759.5 linkuse as main transcript	c.-406+4942G>C		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.183C>G	p.Gly61Gly	synonymous_variant	3/3	1	NM_001014336.2	ENSP00000366234.1		Q6EBC2
LRRC43	ENST00000537729.5 linkuse as main transcript	c.-406+4942G>C		intron_variant		5		ENSP00000438751.1		F5H0N3

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21369

AN:

151956

Hom.:

1774

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0675

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.236

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.0917

Gnomad SAS

AF:

0.229

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.137

GnomAD3 exomes

AF:

0.170

AC:

41354

AN:

243396

Hom.:

3916

AF XY:

0.168

AC XY:

22097

AN XY:

131728

show subpopulations

Gnomad AFR exome

AF:

0.0633

Gnomad AMR exome

AF:

0.284

Gnomad ASJ exome

AF:

0.122

Gnomad EAS exome

AF:

0.101

Gnomad SAS exome

AF:

0.216

Gnomad FIN exome

AF:

0.150

Gnomad NFE exome

AF:

0.157

Gnomad OTH exome

AF:

0.164

GnomAD4 exome

AF:

0.160

AC:

233402

AN:

1457288

Hom.:

19901

Cov.:

AF XY:

0.161

AC XY:

116986

AN XY:

724716

show subpopulations

Gnomad4 AFR exome

AF:

0.0653

Gnomad4 AMR exome

AF:

0.277

Gnomad4 ASJ exome

AF:

0.119

Gnomad4 EAS exome

AF:

0.0836

Gnomad4 SAS exome

AF:

0.214

Gnomad4 FIN exome

AF:

0.151

Gnomad4 NFE exome

AF:

0.159

Gnomad4 OTH exome

AF:

0.153

GnomAD4 genome

AF:

0.141

AC:

21383

AN:

152074

Hom.:

1780

Cov.:

AF XY:

0.143

AC XY:

10621

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.0674

Gnomad4 AMR

AF:

0.237

Gnomad4 ASJ

AF:

0.120

Gnomad4 EAS

AF:

0.0915

Gnomad4 SAS

AF:

0.228

Gnomad4 FIN

AF:

0.149

Gnomad4 NFE

AF:

0.161

Gnomad4 OTH

AF:

0.137

Alfa

AF:

0.103

Hom.:

224

Bravo

AF:

0.139

Asia WGS

AF:

0.161

AC:

562

AN:

3478

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

Feb 21, 2024

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

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.053

DANN

Benign

0.65

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