chr2-113123370-T-C

Variant names:

• chr2-113123370-T-C
• rs315936
• ENST00000259206.9:c.73+3242T>C

Variant summary

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

The NM_173841.3(IL1RN):​c.73+3242T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,108 control chromosomes in the GnomAD database, including 43,828 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 0.76 (43828 hom., cov: 31)
• Consequence: IL1RN NM_173841.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RN	NM_173841.3	c.73+3242T>C		intron_variant	Intron 2 of 5		NP_776213.1
IL1RN	NM_000577.5	c.11-4319T>C		intron_variant	Intron 1 of 4		NP_000568.1
IL1RN	NM_001318914.2	c.-39+1752T>C		intron_variant	Intron 3 of 6		NP_001305843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000259206.9	c.73+3242T>C		intron_variant	Intron 2 of 5	1		ENSP00000259206.5
IL1RN	ENST00000354115.6	c.11-4319T>C		intron_variant	Intron 1 of 4	1		ENSP00000329072.3
IL1RN	ENST00000361779.7	c.-39+1752T>C		intron_variant	Intron 2 of 5	1		ENSP00000354816.3

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115170 AN: 151990 Hom.: 43803 Cov.: 31

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.742

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

GnomAD4 genome AF: 0.758 AC: 115242 AN: 152108 Hom.: 43828 Cov.: 31 AF XY: 0.757 AC XY: 56274 AN XY: 74350

Gnomad4 AFR AF: 0.802

Gnomad4 AMR AF: 0.703

Gnomad4 ASJ AF: 0.712

Gnomad4 EAS AF: 0.923

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.741

Gnomad4 NFE AF: 0.738

Gnomad4 OTH AF: 0.740

Alfa AF: 0.753 Hom.: 5470

Bravo AF: 0.759

Asia WGS AF: 0.801 AC: 2784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.22
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs315936; hg19: chr2-113880947;