rs6761276

chr2-113074735-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173161.3(IL1F10):c.131T>C(p.Ile44Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,610,742 control chromosomes in the GnomAD database, including 267,979 homozygotes. In-silico tool predicts 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 0.57 (24932 hom., cov: 33)
  • Exomes 𝑓: 0.57 (243047 hom.)
• Consequence: IL1F10 NM_173161.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.5109908E-6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1F10	NM_173161.3	c.131T>C	p.Ile44Thr	missense_variant	4/5	ENST00000341010.6
IL1F10	NM_032556.6	c.131T>C	p.Ile44Thr	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1F10	ENST00000341010.6	c.131T>C	p.Ile44Thr	missense_variant	4/5	1	NM_173161.3	P1
IL1F10	ENST00000393197.3	c.131T>C	p.Ile44Thr	missense_variant	3/4	1		P1
IL1F10	ENST00000496265.1	n.197T>C		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86156 AN: 152026 Hom.: 24901 Cov.: 33

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.581

GnomAD3 exomes AF: 0.560 AC: 140726 AN: 251370 Hom.: 41199 AF XY: 0.569 AC XY: 77247 AN XY: 135844

Gnomad AFR exome AF: 0.585

Gnomad AMR exome AF: 0.563

Gnomad ASJ exome AF: 0.570

Gnomad EAS exome AF: 0.170

Gnomad SAS exome AF: 0.689

Gnomad FIN exome AF: 0.552

Gnomad NFE exome AF: 0.583

Gnomad OTH exome AF: 0.574

GnomAD4 exome AF: 0.571 AC: 833354 AN: 1458598 Hom.: 243047 Cov.: 44 AF XY: 0.575 AC XY: 417007 AN XY: 725772

Gnomad4 AFR exome AF: 0.584

Gnomad4 AMR exome AF: 0.564

Gnomad4 ASJ exome AF: 0.564

Gnomad4 EAS exome AF: 0.148

Gnomad4 SAS exome AF: 0.684

Gnomad4 FIN exome AF: 0.548

Gnomad4 NFE exome AF: 0.579

Gnomad4 OTH exome AF: 0.563

GnomAD4 genome AF: 0.567 AC: 86226 AN: 152144 Hom.: 24932 Cov.: 33 AF XY: 0.563 AC XY: 41894 AN XY: 74374

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.657

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.586

Alfa AF: 0.573 Hom.: 66152

Bravo AF: 0.568

TwinsUK AF: 0.588 AC: 2180

ALSPAC AF: 0.575 AC: 2216

ESP6500AA AF: 0.579 AC: 2549

ESP6500EA AF: 0.585 AC: 5034

ExAC AF: 0.564 AC: 68484

Asia WGS AF: 0.479 AC: 1665 AN: 3478

EpiCase AF: 0.589

EpiControl AF: 0.585

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.64
Cadd	Benign	19
Dann	Uncertain	0.99
DEOGEN2	Benign	0.048	T;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.24	N
MetaRNN	Benign	0.0000035	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	0.77	P;P;P
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.034
Sift	Benign	0.036	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.0020	B;B
Vest4		0.081
MPC		0.10
ClinPred		0.020	T
GERP RS		3.9
Varity_R		0.21
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs6761276; hg19: chr2-113832312; COSMIC: COSV61750606;