rs3811047

Variant names:

• chr2-112913833-A-G
• rs3811047
• NM_014439.4:c.124A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-112913833-A-G
• chr2-112913833-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (30741 hom., cov: 31)
  • Exomes 𝑓: 0.70 (364433 hom.)
• Consequence: IL37 NM_014439.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.681
• Publications: 82 publications found

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 Gene-Disease associations (from GenCC):

• inflammatory bowel disease (infantile ulcerative colitis) 31, autosomal recessive

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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	c.124A>G	p.Thr42Ala	missense_variant	Exon 3 of 6	ENST00000263326.8	NP_055254.2
IL37	NM_173204.2	c.124A>G	p.Thr42Ala	missense_variant	Exon 3 of 5		NP_775296.1
IL37	NM_173202.2	c.82+739A>G		intron_variant	Intron 2 of 4		NP_775294.1
IL37	NM_173203.2	c.82+739A>G		intron_variant	Intron 2 of 3		NP_775295.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92524 AN: 151800 Hom.: 30720 Cov.: 31

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

GnomAD2 exomes AF: 0.711 AC: 177949 AN: 250348 AF XY: 0.714

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 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.: 45 AF XY: 0.703 AC XY: 510676 AN XY: 725934

African (AFR) AF: 0.302 AC: 10079 AN: 33424

American (AMR) AF: 0.833 AC: 37220 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 18988 AN: 26094

East Asian (EAS) AF: 0.814 AC: 32265 AN: 39656

South Asian (SAS) AF: 0.732 AC: 63054 AN: 86104

European-Finnish (FIN) AF: 0.719 AC: 38389 AN: 53372

Middle Eastern (MID) AF: 0.635 AC: 3660 AN: 5762

European-Non Finnish (NFE) AF: 0.702 AC: 779510 AN: 1109742

Other (OTH) AF: 0.696 AC: 41953 AN: 60296

GnomAD4 genome AF: 0.609 AC: 92581 AN: 151916 Hom.: 30741 Cov.: 31 AF XY: 0.617 AC XY: 45758 AN XY: 74216

African (AFR) AF: 0.321 AC: 13286 AN: 41410

American (AMR) AF: 0.752 AC: 11501 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2492 AN: 3472

East Asian (EAS) AF: 0.822 AC: 4219 AN: 5130

South Asian (SAS) AF: 0.726 AC: 3498 AN: 4818

European-Finnish (FIN) AF: 0.724 AC: 7630 AN: 10536

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47792 AN: 67944

Other (OTH) AF: 0.640 AC: 1354 AN: 2114

Alfa AF: 0.681 Hom.: 164068

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

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) -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.79	T
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	N
LIST_S2	Benign	0.17	T;T
MetaRNN	Benign	0.0000014	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N;N
PhyloP100		-0.68
PrimateAI	Benign	0.30	T
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	T
GERP RS		1.6
Varity_R		0.020
gMVP		0.071
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3811047; hg19: chr2-113671410; COSMIC: COSV54490369; COSMIC: COSV54490369;