2-112913833-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014439.4(IL37):c.124A>T(p.Thr42Ser) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T42A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL37 NM_014439.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681

Genes affected

IL37 (HGNC:15563): (interleukin 37) The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine can bind to, and may be a ligand for interleukin 18 receptor (IL18R1/IL-1Rrp). This cytokine also binds to interleukin 18 binding protein (IL18BP), an inhibitory binding protein of interleukin 18 (IL18), and subsequently forms a complex with IL18 receptor beta subunit, and through which it inhibits the activity of IL18. This gene along with eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. Five alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

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=0.0450311).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL37	NM_014439.4	c.124A>T	p.Thr42Ser	missense_variant	3/6	ENST00000263326.8
IL37	NM_173204.2	c.124A>T	p.Thr42Ser	missense_variant	3/5
IL37	NM_173202.2	c.82+739A>T		intron_variant
IL37	NM_173203.2	c.82+739A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL37	ENST00000263326.8	c.124A>T	p.Thr42Ser	missense_variant	3/6	1	NM_014439.4	P1
IL37	ENST00000353225.7	c.124A>T	p.Thr42Ser	missense_variant	2/4	1
IL37	ENST00000349806.7	c.82+739A>T		intron_variant		1
IL37	ENST00000352179.7	c.82+739A>T		intron_variant		1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461192 Hom.: 0 Cov.: 45 AF XY: 0.00 AC XY: 0 AN XY: 726934

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.0090
Dann	Benign	0.10
DEOGEN2	Benign	0.00017	T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00033	N
LIST_S2	Benign	0.16	T;T
M_CAP	Benign	0.00065	T
MetaRNN	Benign	0.045	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.97	N;N
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.49	N;N
REVEL	Benign	0.034
Sift	Benign	1.0	T;T
Sift4G	Benign	0.89	T;T
Polyphen		0.0	B;B
Vest4		0.050
MutPred		0.20		Loss of glycosylation at T42 (P = 0.0114);Loss of glycosylation at T42 (P = 0.0114);
MVP		0.048
MPC		0.077
ClinPred		0.044	T
GERP RS		1.6
Varity_R		0.020
gMVP		0.050

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs3811047; hg19: chr2-113671410;