12-122172836-C-G

Position:

• chr12-122172836-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000377035.2(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 ENST00000377035.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
IL31	NM_001014336.2	c.166-95G>C		intron_variant		ENST00000377035.2	NP_001014358.1
LRRC43	NM_152759.5	c.-406+5054C>G		intron_variant			NP_689972.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL31	ENST00000377035.2	c.166-95G>C		intron_variant		1	NM_001014336.2	ENSP00000366234	P1
LRRC43	ENST00000537729.5	c.-406+5054C>G		intron_variant		5		ENSP00000438751

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

Gnomad4 AFR exome AF: 0.0844

Gnomad4 AMR exome AF: 0.267

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.0797

Gnomad4 SAS exome AF: 0.212

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.145

Gnomad4 OTH exome AF: 0.144

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

Gnomad4 AFR AF: 0.0866

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.0923

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.142

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
DANN	Benign	0.28

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

Other links and lift over

dbSNP: rs7977932; hg19: chr12-122657383;