Genetic Variant IL31:c.166-95G>A (chr12-122172836-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001014336.2(IL31):c.166-95G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000126 in 792,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000013 ( 0 hom. )

Consequence

IL31
NM_001014336.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0660

Publications

23 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL31	NM_001014336.2 link	c.166-95G>A		intron_variant	Intron 2 of 2	ENST00000377035.2	NP_001014358.1	Q6EBC2
LRRC43	NM_152759.5 link	c.-406+5054C>T		intron_variant	Intron 1 of 11		NP_689972.3	Q8N309-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL31	ENST00000377035.2 link	c.166-95G>A		intron_variant	Intron 2 of 2	1	NM_001014336.2	ENSP00000366234.1		Q6EBC2
LRRC43	ENST00000537729.5 link	c.-406+5054C>T		intron_variant	Intron 1 of 5	5		ENSP00000438751.1		F5H0N3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000126

AC:

AN:

792436

Hom.:

AF XY:

0.00000248

AC XY:

AN XY:

402710

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19180

American (AMR)

AF:

0.00

AC:

AN:

24968

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17046

East Asian (EAS)

AF:

0.00

AC:

AN:

32852

South Asian (SAS)

AF:

0.00

AC:

AN:

54664

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44998

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2666

European-Non Finnish (NFE)

AF:

0.00000179

AC:

AN:

558890

Other (OTH)

AF:

0.00

AC:

AN:

37172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.1

(source)

DANN

Benign

0.93

PhyloP100

0.066

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over