rs878972

Variant names:

• chr2-113120136-A-C
• rs878972
• ENST00000259206.9:c.73+8A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-113120136-A-C
• chr2-113120136-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173841.3(IL1RN):​c.73+8A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,604,640 control chromosomes in the GnomAD database, including 56,618 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4070 hom., cov: 30)
  • Exomes 𝑓: 0.26 (52548 hom.)
• Consequence: IL1RN NM_173841.3 splice_region, intron
• Scores: Splicing: ADA: 0.00002619
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.149
• Publications: 15 publications found

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]

IL1RN Gene-Disease associations (from GenCC):

• sterile multifocal osteomyelitis with periostitis and pustulosis

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 2-113120136-A-C is Benign according to our data. Variant chr2-113120136-A-C is described in ClinVar as Benign. ClinVar VariationId is 330822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173841.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RN	NM_173841.3		c.73+8A>C		splice_region intron	N/A	NP_776213.1	P18510-3
	IL1RN	NM_000577.5		c.10+2108A>C		intron	N/A	NP_000568.1	P18510-2
	IL1RN	NM_001318914.2		c.-210+8A>C		splice_region intron	N/A	NP_001305843.1	P18510-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RN	ENST00000259206.9	TSL:1	c.73+8A>C		splice_region intron	N/A	ENSP00000259206.5	P18510-3
	IL1RN	ENST00000354115.6	TSL:1	c.10+2108A>C		intron	N/A	ENSP00000329072.3	P18510-2
	IL1RN	ENST00000361779.7	TSL:1	c.-209-1312A>C		intron	N/A	ENSP00000354816.3	P18510-4

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31746 AN: 151264 Hom.: 4064 Cov.: 30

Gnomad AFR AF: 0.0610

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.229

GnomAD2 exomes AF: 0.253 AC: 63662 AN: 251238 AF XY: 0.256

Gnomad AFR exome AF: 0.0536

Gnomad AMR exome AF: 0.317

Gnomad ASJ exome AF: 0.295

Gnomad EAS exome AF: 0.0945

Gnomad FIN exome AF: 0.304

Gnomad NFE exome AF: 0.266

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.263 AC: 382285 AN: 1453256 Hom.: 52548 Cov.: 29 AF XY: 0.263 AC XY: 190375 AN XY: 723634

African (AFR) AF: 0.0499 AC: 1664 AN: 33340

American (AMR) AF: 0.313 AC: 13981 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 7472 AN: 26076

East Asian (EAS) AF: 0.101 AC: 3990 AN: 39668

South Asian (SAS) AF: 0.282 AC: 24268 AN: 86086

European-Finnish (FIN) AF: 0.298 AC: 15917 AN: 53408

Middle Eastern (MID) AF: 0.218 AC: 1244 AN: 5696

European-Non Finnish (NFE) AF: 0.270 AC: 298606 AN: 1104170

Other (OTH) AF: 0.252 AC: 15143 AN: 60100

GnomAD4 genome AF: 0.210 AC: 31763 AN: 151384 Hom.: 4070 Cov.: 30 AF XY: 0.212 AC XY: 15694 AN XY: 73864

African (AFR) AF: 0.0609 AC: 2512 AN: 41244

American (AMR) AF: 0.275 AC: 4172 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 994 AN: 3470

East Asian (EAS) AF: 0.104 AC: 540 AN: 5174

South Asian (SAS) AF: 0.288 AC: 1376 AN: 4772

European-Finnish (FIN) AF: 0.303 AC: 3157 AN: 10404

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18242 AN: 67856

Other (OTH) AF: 0.231 AC: 485 AN: 2102

Alfa AF: 0.239 Hom.: 2870

Bravo AF: 0.199

Asia WGS AF: 0.202 AC: 703 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	not provided (2)
-	-	2	Sterile multifocal osteomyelitis with periostitis and pustulosis (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.0
DANN	Benign	0.37
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000026
dbscSNV1_RF	Benign	0.0

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

Other links and lift over

dbSNP: rs878972; hg19: chr2-113877713; COSMIC: COSV52080718; COSMIC: COSV52080718;