12-122173846-C-T

Variant names:

• chr12-122173846-C-T
• NM_001014336.2:c.163G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001014336.2(IL31):​c.163G>A​(p.Asp55Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL31 NM_001014336.2 missense, splice_region
• Scores: Splicing: ADA: 0.00007462
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.55
• Publications: 0 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: 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 (MetaRNN=0.06023115).

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.163G>A	p.Asp55Asn	missense splice_region	Exon 2 of 3	NP_001014358.1	Q6EBC2
	LRRC43	NM_152759.5		c.-406+6064C>T		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.163G>A	p.Asp55Asn	missense splice_region	Exon 2 of 3	ENSP00000366234.1	Q6EBC2
	LRRC43	ENST00000537729.5	TSL:5	c.-406+6064C>T		intron	N/A	ENSP00000438751.1	F5H0N3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.18
DANN	Benign	0.91
DEOGEN2	Benign	0.073	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0065	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.00091	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-1.5
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.015
Sift	Benign	0.21	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.023	B
Vest4		0.20
MutPred		0.22		Gain of methylation at K54 (P = 0.0638)
MVP		0.081
MPC		0.43
ClinPred		0.073	T
GERP RS		-3.0
PromoterAI		0.023	Neutral
Varity_R		0.035
gMVP		0.23
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000075
dbscSNV1_RF	Benign	0.0020
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

Other links and lift over

hg19: chr12-122658393;