12-122172836-C-G

Variant names:

• chr12-122172836-C-G
• rs7977932
• NM_001014336.2:c.166-95G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660
• Publications: 23 publications found

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]

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001014336.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL31	NM_001014336.2	MANE Select	c.166-95G>C		intron	N/A	NP_001014358.1	Q6EBC2
	LRRC43	NM_152759.5		c.-406+5054C>G		intron	N/A	NP_689972.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL31	ENST00000377035.2	TSL:1 MANE Select	c.166-95G>C		intron	N/A	ENSP00000366234.1	Q6EBC2
	LRRC43	ENST00000537729.5	TSL:5	c.-406+5054C>G		intron	N/A	ENSP00000438751.1	F5H0N3

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22262 AN: 151982 Hom.: 1851 Cov.: 32

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

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

GnomAD4 genome AF: 0.146 AC: 22280 AN: 152100 Hom.: 1857 Cov.: 32 AF XY: 0.149 AC XY: 11047 AN XY: 74344

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: 23 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10981 AN: 67996

Other (OTH) AF: 0.142 AC: 301 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.28
PhyloP100		0.066
Mutation Taster		=100/0	polymorphism (auto)

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.

Other links and lift over

dbSNP: rs7977932;

hg19: chr12-122657383;

COSMIC: COSV107487939;