rs3811047

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014439.4(IL37):c.124A>G(p.Thr42Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 1,611,040 control chromosomes in the GnomAD database, including 395,174 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.61 ( 30741 hom., cov: 31)

Exomes 𝑓: 0.70 ( 364433 hom. )

Consequence

IL37
NM_014439.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.681

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.4006786E-6).

BP6

Variant 2-112913833-A-G is Benign according to our data. Variant chr2-112913833-A-G is described in ClinVar as [Benign]. Clinvar id is 767816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL37	NM_014439.4 link	c.124A>G	p.Thr42Ala	missense_variant	Exon 3 of 6	ENST00000263326.8	NP_055254.2	Q9NZH6-1
IL37	NM_173204.2 link	c.124A>G	p.Thr42Ala	missense_variant	Exon 3 of 5		NP_775296.1	Q9NZH6-3
IL37	NM_173202.2 link	c.82+739A>G		intron_variant	Intron 2 of 4		NP_775294.1	Q9NZH6-4
IL37	NM_173203.2 link	c.82+739A>G		intron_variant	Intron 2 of 3		NP_775295.1	Q9NZH6-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL37	ENST00000263326.8 link	c.124A>G	p.Thr42Ala	missense_variant	Exon 3 of 6	1	NM_014439.4	ENSP00000263326.3	Q9NZH6-1
IL37	ENST00000353225.7 link	c.124A>G	p.Thr42Ala	missense_variant	Exon 2 of 4	1		ENSP00000309208.3	Q9NZH6-3
IL37	ENST00000352179.7 link	c.82+739A>G		intron_variant	Intron 1 of 3	1		ENSP00000263327.3	Q9NZH6-4
IL37	ENST00000349806.7 link	c.82+739A>G		intron_variant	Intron 1 of 2	1		ENSP00000263328.3	Q9NZH6-5

Frequencies

GnomAD3 genomes

AF:

0.610

AC:

92524

AN:

151800

Hom.:

30720

Cov.:

show subpopulations

Gnomad AFR

AF:

0.321

Gnomad AMI

AF:

0.690

Gnomad AMR

AF:

0.751

Gnomad ASJ

AF:

0.718

Gnomad EAS

AF:

0.822

Gnomad SAS

AF:

0.725

Gnomad FIN

AF:

0.724

Gnomad MID

AF:

0.623

Gnomad NFE

AF:

0.703

Gnomad OTH

AF:

0.639

GnomAD3 exomes

AF:

0.711

AC:

177949

AN:

250348

Hom.:

65289

AF XY:

0.714

AC XY:

96566

AN XY:

135320

show subpopulations

Gnomad AFR exome

AF:

0.309

Gnomad AMR exome

AF:

0.843

Gnomad ASJ exome

AF:

0.729

Gnomad EAS exome

AF:

0.827

Gnomad SAS exome

AF:

0.730

Gnomad FIN exome

AF:

0.728

Gnomad NFE exome

AF:

0.699

Gnomad OTH exome

AF:

0.713

GnomAD4 exome

AF:

0.703

AC:

1025118

AN:

1459124

Hom.:

364433

Cov.:

AF XY:

0.703

AC XY:

510676

AN XY:

725934

show subpopulations

Gnomad4 AFR exome

AF:

0.302

Gnomad4 AMR exome

AF:

0.833

Gnomad4 ASJ exome

AF:

0.728

Gnomad4 EAS exome

AF:

0.814

Gnomad4 SAS exome

AF:

0.732

Gnomad4 FIN exome

AF:

0.719

Gnomad4 NFE exome

AF:

0.702

Gnomad4 OTH exome

AF:

0.696

GnomAD4 genome

AF:

0.609

AC:

92581

AN:

151916

Hom.:

30741

Cov.:

AF XY:

0.617

AC XY:

45758

AN XY:

74216

show subpopulations

Gnomad4 AFR

AF:

0.321

Gnomad4 AMR

AF:

0.752

Gnomad4 ASJ

AF:

0.718

Gnomad4 EAS

AF:

0.822

Gnomad4 SAS

AF:

0.726

Gnomad4 FIN

AF:

0.724

Gnomad4 NFE

AF:

0.703

Gnomad4 OTH

AF:

0.640

Alfa

AF:

0.691

Hom.:

91018

Bravo

AF:

0.600

TwinsUK

AF:

0.714

AC:

2646

ALSPAC

AF:

0.700

AC:

2698

ESP6500AA

AF:

0.321

AC:

1415

ESP6500EA

AF:

0.701

AC:

6032

ExAC

AF:

0.694

AC:

84227

Asia WGS

AF:

0.739

AC:

2569

AN:

3478

EpiCase

AF:

0.704

EpiControl

AF:

0.700

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 18, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27775096) -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.65

DANN

Benign

0.55

DEOGEN2

Benign

0.00024

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0049

LIST_S2

Benign

0.17

T;T

MetaRNN

Benign

0.0000014

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.21

N;N

REVEL

Benign

0.053

Sift

Benign

0.53

T;T

Sift4G

Benign

0.57

T;T

Polyphen

0.0

B;B

Vest4

0.019

MPC

0.084

ClinPred

0.00068

GERP RS

1.6

Varity_R

0.020

gMVP

0.071

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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