rs4251961

Positions:

• chr2-113116890-T-C

Variant summary

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

The XM_011511121.2(IL1RN):​c.-272-3176T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,158 control chromosomes in the GnomAD database, including 7,431 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 0.29 (7431 hom., cov: 32)
• Consequence: IL1RN XM_011511121.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52

Genes affected

IL1RN (HGNC:6000): (interleukin 1 receptor antagonist) The protein encoded by this gene is a member of the interleukin 1 cytokine family. This protein inhibits the activities of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B), and modulates a variety of interleukin 1 related immune and inflammatory responses, particularly in the acute phase of infection and inflammation. This gene and five other closely related cytokine genes form a gene cluster spanning approximately 400 kb on chromosome 2. A polymorphism of this gene is reported to be associated with increased risk of osteoporotic fractures and gastric cancer. Several alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Aug 2020]

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 (SAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RN	XM_011511121.2	c.-272-3176T>C		intron_variant			XP_011509423.1
IL1RN	XM_047444184.1	c.-272-3176T>C		intron_variant			XP_047300140.1
IL1RN	XM_047444185.1	c.-401-647T>C		intron_variant			XP_047300141.1
IL1RN	XM_047444186.1	c.-210+3776T>C		intron_variant			XP_047300142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000409052.6	c.-272-3176T>C		intron_variant, NMD_transcript_variant		5		ENSP00000387210
IL1RN	ENST00000465812.6	n.647-647T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44870 AN: 152040 Hom.: 7426 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.0869

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.295 AC: 44884 AN: 152158 Hom.: 7431 Cov.: 32 AF XY: 0.291 AC XY: 21638 AN XY: 74384

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.0871

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.333

Alfa AF: 0.358 Hom.: 10295

Bravo AF: 0.290

Asia WGS AF: 0.278 AC: 965 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	0.021
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4251961; hg19: chr2-113874467;