Genetic Variant NM_001014336.2:c.166-95G>C (chr12-122172836-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001014336.2(IL31):c.166-95G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 943,210 control chromosomes in the GnomAD database, including 11,652 homozygotes. 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: 𝑓 0.15 ( 1857 hom., cov: 32)

Exomes 𝑓: 0.15 ( 9795 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL31	NM_001014336.2 link	c.166-95G>C		intron_variant	Intron 2 of 2	ENST00000377035.2	NP_001014358.1	Q6EBC2
LRRC43	NM_152759.5 link	c.-406+5054C>G		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>C		intron_variant	Intron 2 of 2	1	NM_001014336.2	ENSP00000366234.1		Q6EBC2
LRRC43	ENST00000537729.5 link	c.-406+5054C>G		intron_variant	Intron 1 of 5	5		ENSP00000438751.1		F5H0N3

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22262

AN:

151982

Hom.:

1851

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0866

Gnomad AMI

AF:

0.145

Gnomad AMR

AF:

0.240

Gnomad ASJ

AF:

0.119

Gnomad EAS

AF:

0.0925

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.143

GnomAD4 exome

AF:

0.149

AC:

117712

AN:

791110

Hom.:

9795

AF XY:

0.151

AC XY:

60736

AN XY:

402002

show subpopulations

African (AFR)

AF:

0.0844

AC:

1618

AN:

19178

American (AMR)

AF:

0.267

AC:

6670

AN:

24944

Ashkenazi Jewish (ASJ)

AF:

0.116

AC:

1980

AN:

17034

East Asian (EAS)

AF:

0.0797

AC:

2618

AN:

32850

South Asian (SAS)

AF:

0.212

AC:

11585

AN:

54628

European-Finnish (FIN)

AF:

0.151

AC:

6768

AN:

44956

Middle Eastern (MID)

AF:

0.0917

AC:

244

AN:

2662

European-Non Finnish (NFE)

AF:

0.145

AC:

80887

AN:

557740

Other (OTH)

AF:

0.144

AC:

5342

AN:

37118

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

5070

10139

15209

20278

25348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2024

4048

6072

8096

10120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.146

AC:

22280

AN:

152100

Hom.:

1857

Cov.:

AF XY:

0.149

AC XY:

11047

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0866

AC:

3594

AN:

41506

American (AMR)

AF:

0.241

AC:

3673

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

413

AN:

3468

East Asian (EAS)

AF:

0.0923

AC:

478

AN:

5176

South Asian (SAS)

AF:

0.230

AC:

1111

AN:

4820

European-Finnish (FIN)

AF:

0.149

AC:

1575

AN:

10560

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.161

AC:

10981

AN:

67996

Other (OTH)

AF:

0.142

AC:

301

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

967

1933

2900

3866

4833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

248

496

744

992

1240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0784

Hom.:

119

Bravo

AF:

0.145

Asia WGS

AF:

0.166

AC:

580

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

1.7

(source)

DANN

Benign

0.28

PhyloP100

0.066

Mutation Taster

=100/0

polymorphism (auto)

(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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over