rs1194330719

Variant names:

• chr2-102172779-C-A
• rs1194330719
• NM_000877.4:c.932C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-102172779-C-A
• chr2-102172779-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000877.4(IL1R1):​c.932C>A​(p.Thr311Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,142 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T311I) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: IL1R1 NM_000877.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.825
• Publications: 1 publications found

Genes affected

IL1R1 (HGNC:5993): (interleukin 1 receptor type 1) This gene encodes a cytokine receptor that belongs to the interleukin-1 receptor family. The encoded protein is a receptor for interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist. It is an important mediator involved in many cytokine-induced immune and inflammatory responses. This gene is located in a cluster of related cytokine receptor genes on chromosome 2q12. [provided by RefSeq, Dec 2013]

IL1R1-AS1 (HGNC:53898): (IL1R1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28106534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1R1	NM_000877.4	c.932C>A	p.Thr311Asn	missense_variant	Exon 9 of 12	ENST00000410023.6	NP_000868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1R1	ENST00000410023.6	c.932C>A	p.Thr311Asn	missense_variant	Exon 9 of 12	1	NM_000877.4	ENSP00000386380.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152142 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 28

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152142 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74320

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2094

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.94
DEOGEN2	Benign	0.032	T;.;.;T;.;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.75	T;.;.;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.28	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.4	.;.;.;.;.;M
PhyloP100		-0.82
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.5	D;D;D;N;D;D
REVEL	Benign	0.13
Sift	Uncertain	0.016	D;D;D;D;D;D
Sift4G	Uncertain	0.026	D;D;D;D;D;D
Polyphen		0.97	D;D;D;.;D;B
Vest4		0.33
MutPred		0.42		Loss of methylation at K307 (P = 0.0939);Loss of methylation at K307 (P = 0.0939);Loss of methylation at K307 (P = 0.0939);.;Loss of methylation at K307 (P = 0.0939);Loss of methylation at K307 (P = 0.0939);
MVP		0.22
MPC		0.86
ClinPred		0.73	D
GERP RS		-6.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.42
gMVP		0.74
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1194330719; hg19: chr2-102789239;