Variant chr2-112913801-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_014439.4(IL37):c.92G>T(p.Gly31Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 1,610,358 control chromosomes in the GnomAD database, including 393,215 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.59 ( 30082 hom., cov: 32)

Exomes 𝑓: 0.70 ( 363133 hom. )

Consequence

IL37
NM_014439.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.51

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 Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL37	NM_014439.4 linkuse as main transcript	c.92G>T	p.Gly31Val	missense_variant	3/6	ENST00000263326.8	NP_055254.2	Q9NZH6-1
IL37	NM_173204.2 linkuse as main transcript	c.92G>T	p.Gly31Val	missense_variant	3/5		NP_775296.1	Q9NZH6-3
IL37	NM_173202.2 linkuse as main transcript	c.82+707G>T		intron_variant			NP_775294.1	Q9NZH6-4
IL37	NM_173203.2 linkuse as main transcript	c.82+707G>T		intron_variant			NP_775295.1	Q9NZH6-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IL37	ENST00000263326.8 linkuse as main transcript	c.92G>T	p.Gly31Val	missense_variant	3/6	1	NM_014439.4	ENSP00000263326.3	Q9NZH6-1
IL37	ENST00000353225.7 linkuse as main transcript	c.92G>T	p.Gly31Val	missense_variant	2/4	1		ENSP00000309208.3	Q9NZH6-3
IL37	ENST00000352179.7 linkuse as main transcript	c.82+707G>T		intron_variant		1		ENSP00000263327.3	Q9NZH6-4
IL37	ENST00000349806.7 linkuse as main transcript	c.82+707G>T		intron_variant		1		ENSP00000263328.3	Q9NZH6-5

Frequencies

GnomAD3 genomes

AF:

0.595

AC:

90359

AN:

151966

Hom.:

30065

Cov.:

show subpopulations

Gnomad AFR

AF:

0.270

Gnomad AMI

AF:

0.692

Gnomad AMR

AF:

0.745

Gnomad ASJ

AF:

0.715

Gnomad EAS

AF:

0.823

Gnomad SAS

AF:

0.725

Gnomad FIN

AF:

0.725

Gnomad MID

AF:

0.623

Gnomad NFE

AF:

0.703

Gnomad OTH

AF:

0.631

GnomAD3 exomes

AF:

0.707

AC:

176516

AN:

249698

Hom.:

64875

AF XY:

0.711

AC XY:

95880

AN XY:

134910

show subpopulations

Gnomad AFR exome

AF:

0.255

Gnomad AMR exome

AF:

0.840

Gnomad ASJ exome

AF:

0.727

Gnomad EAS exome

AF:

0.828

Gnomad SAS exome

AF:

0.731

Gnomad FIN exome

AF:

0.727

Gnomad NFE exome

AF:

0.699

Gnomad OTH exome

AF:

0.712

GnomAD4 exome

AF:

0.701

AC:

1021735

AN:

1458274

Hom.:

363133

Cov.:

AF XY:

0.702

AC XY:

509086

AN XY:

725480

show subpopulations

Gnomad4 AFR exome

AF:

0.248

Gnomad4 AMR exome

AF:

0.830

Gnomad4 ASJ exome

AF:

0.725

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:

0.692

GnomAD4 genome

AF:

0.594

AC:

90402

AN:

152084

Hom.:

30082

Cov.:

AF XY:

0.602

AC XY:

44774

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.270

Gnomad4 AMR

AF:

0.746

Gnomad4 ASJ

AF:

0.715

Gnomad4 EAS

AF:

0.823

Gnomad4 SAS

AF:

0.725

Gnomad4 FIN

AF:

0.725

Gnomad4 NFE

AF:

0.703

Gnomad4 OTH

AF:

0.632

Alfa

AF:

0.671

Hom.:

46288

Bravo

AF:

0.583

TwinsUK

AF:

0.714

AC:

2646

ALSPAC

AF:

0.699

AC:

2693

ESP6500AA

AF:

0.280

AC:

1234

ESP6500EA

AF:

0.707

AC:

6080

ExAC

AF:

0.689

AC:

83670

Asia WGS

AF:

0.736

AC:

2559

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.0011

T;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.54

T;T

MetaRNN

Benign

0.0000013

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.20

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

0.10

N;N

REVEL

Benign

0.12

Sift

Benign

0.21

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.87

P;P

Vest4

0.074

MPC

0.11

ClinPred

0.013

GERP RS

1.9

Varity_R

0.078

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.25

Position offset: -9

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over