Variant chr2-112913047-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014439.4(IL37):c.35T>C(p.Met12Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

IL37
NM_014439.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.971

Variant links:

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]

IL37 links:

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ACMG classification

Classification made for transcript

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=0.025334746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
IL37	NM_014439.4 linkuse as main transcript	c.35T>C	p.Met12Thr	missense_variant	2/6	ENST00000263326.8	NP_055254.2
IL37	NM_173202.2 linkuse as main transcript	c.35T>C	p.Met12Thr	missense_variant	2/5		NP_775294.1
IL37	NM_173204.2 linkuse as main transcript	c.35T>C	p.Met12Thr	missense_variant	2/5		NP_775296.1
IL37	NM_173203.2 linkuse as main transcript	c.35T>C	p.Met12Thr	missense_variant	2/4		NP_775295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL37	ENST00000263326.8 linkuse as main transcript	c.35T>C	p.Met12Thr	missense_variant	2/6	1	NM_014439.4	ENSP00000263326	P1	Q9NZH6-1
IL37	ENST00000352179.7 linkuse as main transcript	c.35T>C	p.Met12Thr	missense_variant	1/4	1		ENSP00000263327		Q9NZH6-4
IL37	ENST00000353225.7 linkuse as main transcript	c.35T>C	p.Met12Thr	missense_variant	1/4	1		ENSP00000309208		Q9NZH6-3
IL37	ENST00000349806.7 linkuse as main transcript	c.35T>C	p.Met12Thr	missense_variant	1/3	1		ENSP00000263328		Q9NZH6-5

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 04, 2024

The c.35T>C (p.M12T) alteration is located in exon 1 (coding exon 1) of the IL37 gene. This alteration results from a T to C substitution at nucleotide position 35, causing the methionine (M) at amino acid position 12 to be replaced by a threonine (T). 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

0.15

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

1.5

DANN

Benign

0.42

DEOGEN2

Benign

0.0011

T;.;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0098

LIST_S2

Benign

0.41

T;T;T;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.025

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.63

N;N;N;N

REVEL

Benign

0.010

Sift

Benign

0.41

T;T;T;T

Sift4G

Benign

0.87

T;T;T;T

Polyphen

0.0020

B;B;B;B

Vest4

0.11

MutPred

0.15

Gain of methylation at K11 (P = 0.0348);Gain of methylation at K11 (P = 0.0348);Gain of methylation at K11 (P = 0.0348);Gain of methylation at K11 (P = 0.0348);

MVP

0.10

MPC

0.099

ClinPred

0.013

GERP RS

-2.5

Varity_R

0.056

gMVP

0.057

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over