2-102154278-A-G

Position:

• chr2-102154278-A-G

Variant summary

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

The NM_000877.4(IL1R1):​c.-7+261A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 152,014 control chromosomes in the GnomAD database, including 14,471 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 0.41 (14471 hom., cov: 32)
• Consequence: IL1R1 NM_000877.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.97

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1R1	NM_000877.4	c.-7+261A>G		intron_variant		ENST00000410023.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1R1	ENST00000410023.6	c.-7+261A>G		intron_variant		1	NM_000877.4	P1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62313 AN: 151896 Hom.: 14432 Cov.: 32

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.411 AC: 62416 AN: 152014 Hom.: 14471 Cov.: 32 AF XY: 0.409 AC XY: 30364 AN XY: 74306

Gnomad4 AFR AF: 0.644

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.384

Alfa AF: 0.335 Hom.: 10291

Bravo AF: 0.423

Asia WGS AF: 0.415 AC: 1444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.55
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs2287049; hg19: chr2-102770738; COSMIC: COSV52105312;