rs949963

chr2-102153326-C-T

Variant summary

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

The NM_000877.4(IL1R1):c.-83-615C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,074 control chromosomes in the GnomAD database, including 4,094 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.

• Frequency: Genomes: 𝑓 0.22 (4094 hom., cov: 32)
• Consequence: IL1R1 NM_000877.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.765

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1R1	NM_000877.4	c.-83-615C>T		intron_variant		ENST00000410023.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1R1	ENST00000410023.6	c.-83-615C>T		intron_variant		1	NM_000877.4	P1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33922 AN: 151956 Hom.: 4083 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.217

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.223 AC: 33974 AN: 152074 Hom.: 4094 Cov.: 32 AF XY: 0.223 AC XY: 16610 AN XY: 74326

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.214

Alfa AF: 0.193 Hom.: 6111

Bravo AF: 0.219

Asia WGS AF: 0.265 AC: 923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.2
Dann	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs949963; hg19: chr2-102769786; COSMIC: COSV52105301; COSMIC: COSV52105301;