dbSNP rs6761276: IL1F10:p.Ile44Lys (chr2-113074735-T-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_173161.3(IL1F10):c.131T>A(p.Ile44Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

IL1F10
NM_173161.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.04

Publications

0 publications found

Variant links:

Genes affected

IL1F10 (HGNC:15552): (interleukin 1 family member 10) The protein encoded by this gene is a member of the interleukin 1 cytokine family. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. This cytokine is thought to participate in a network of interleukin 1 family members to regulate adapted and innate immune responses. Two alternatively spliced transcript variants encoding the same protein have been reported. [provided by RefSeq, Jul 2008]

IL1F10 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.926

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1F10	NM_173161.3 link	c.131T>A	p.Ile44Lys	missense_variant	Exon 4 of 5	ENST00000341010.6	NP_775184.1	Q8WWZ1-1
IL1F10	NM_032556.6 link	c.131T>A	p.Ile44Lys	missense_variant	Exon 3 of 4		NP_115945.4	Q8WWZ1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL1F10	ENST00000341010.6 link	c.131T>A	p.Ile44Lys	missense_variant	Exon 4 of 5	1	NM_173161.3	ENSP00000341794.2	Q8WWZ1-1
IL1F10	ENST00000393197.3 link	c.131T>A	p.Ile44Lys	missense_variant	Exon 3 of 4	1		ENSP00000376893.2	Q8WWZ1-1
IL1F10	ENST00000496265.1 link	n.197T>A		non_coding_transcript_exon_variant	Exon 1 of 2	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461112

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726910

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111338

Other (OTH)

AF:

0.00

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.080

T;T

Eigen

Benign

0.013

Eigen_PC

Benign

-0.0049

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.67

.;T

M_CAP

Benign

0.028

MetaRNN

Pathogenic

0.93

D;D

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.7

M;M

PhyloP100

1.0

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.6

D;D

REVEL

Benign

0.16

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.40

B;B

Vest4

0.66

MutPred

0.77

Loss of catalytic residue at P46 (P = 0.0288);Loss of catalytic residue at P46 (P = 0.0288);

MVP

0.34

MPC

0.25

ClinPred

0.89

GERP RS

3.9

Varity_R

0.72

gMVP

0.74

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over