2-113119918-G-T

Variant names:

• chr2-113119918-G-T
• rs928940
• ENST00000259206.9:c.11-148G>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173841.3(IL1RN):​c.11-148G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 713,060 control chromosomes in the GnomAD database, including 243,236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (46968 hom., cov: 29)
  • Exomes 𝑓: 0.83 (196268 hom.)
• Consequence: IL1RN NM_173841.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0880

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-113119918-G-T is Benign according to our data. Variant chr2-113119918-G-T is described in ClinVar as [Benign]. Clinvar id is 1266807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RN	NM_173841.3	c.11-148G>T		intron_variant	Intron 1 of 5		NP_776213.1
IL1RN	NM_000577.5	c.10+1890G>T		intron_variant	Intron 1 of 4		NP_000568.1
IL1RN	NM_001318914.2	c.-272-148G>T		intron_variant	Intron 1 of 6		NP_001305843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000259206.9	c.11-148G>T		intron_variant	Intron 1 of 5	1		ENSP00000259206.5
IL1RN	ENST00000354115.6	c.10+1890G>T		intron_variant	Intron 1 of 4	1		ENSP00000329072.3
IL1RN	ENST00000361779.7	c.-209-1530G>T		intron_variant	Intron 1 of 5	1		ENSP00000354816.3

Frequencies

GnomAD3 genomes AF: 0.777 AC: 117834 AN: 151674 Hom.: 46938 Cov.: 29

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.805

GnomAD4 exome AF: 0.828 AC: 464765 AN: 561268 Hom.: 196268 AF XY: 0.833 AC XY: 248211 AN XY: 297824

Gnomad4 AFR exome AF: 0.617

Gnomad4 AMR exome AF: 0.831

Gnomad4 ASJ exome AF: 0.883

Gnomad4 EAS exome AF: 0.418

Gnomad4 SAS exome AF: 0.884

Gnomad4 FIN exome AF: 0.762

Gnomad4 NFE exome AF: 0.874

Gnomad4 OTH exome AF: 0.827

GnomAD4 genome AF: 0.777 AC: 117911 AN: 151792 Hom.: 46968 Cov.: 29 AF XY: 0.773 AC XY: 57327 AN XY: 74176

Gnomad4 AFR AF: 0.618

Gnomad4 AMR AF: 0.841

Gnomad4 ASJ AF: 0.883

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.878

Gnomad4 FIN AF: 0.753

Gnomad4 NFE AF: 0.872

Gnomad4 OTH AF: 0.807

Alfa AF: 0.765 Hom.: 6009

Bravo AF: 0.771

Asia WGS AF: 0.687 AC: 2389 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs928940; hg19: chr2-113877495; COSMIC: COSV52081479; COSMIC: COSV52081479;