12-122173846-C-T

Position:

• chr12-122173846-C-T

Variant summary

Our verdict is Likely benign. Variant got -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. 17/22 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

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06023115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL31	NM_001014336.2	c.163G>A	p.Asp55Asn	missense_variant, splice_region_variant	2/3	ENST00000377035.2	NP_001014358.1
LRRC43	NM_152759.5	c.-406+6064C>T		intron_variant			NP_689972.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL31	ENST00000377035.2	c.163G>A	p.Asp55Asn	missense_variant, splice_region_variant	2/3	1	NM_001014336.2	ENSP00000366234.1
LRRC43	ENST00000537729.5	c.-406+6064C>T		intron_variant		5		ENSP00000438751.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2023

The c.163G>A (p.D55N) alteration is located in exon 2 (coding exon 2) of the IL31 gene. This alteration results from a G to A substitution at nucleotide position 163, causing the aspartic acid (D) at amino acid position 55 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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
Varity_R		0.035
gMVP		0.23

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-122658393;