chr2-113131323-T-A

Position:

• chr2-113131323-T-A

Variant summary

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

The NM_173842.3(IL1RN):​c.318+166T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 152,062 control chromosomes in the GnomAD database, including 27,520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.58 (27520 hom., cov: 32)
• Consequence: IL1RN NM_173842.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0900

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=-0.85).
• BP6: Variant 2-113131323-T-A is Benign according to our data. Variant chr2-113131323-T-A is described in ClinVar as [Benign]. Clinvar id is 1251642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RN	NM_173842.3	c.318+166T>A		intron_variant		ENST00000409930.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RN	ENST00000409930.4	c.318+166T>A		intron_variant		1	NM_173842.3	P4

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87410 AN: 151944 Hom.: 27498 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.710

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.575 AC: 87476 AN: 152062 Hom.: 27520 Cov.: 32 AF XY: 0.578 AC XY: 42961 AN XY: 74338

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.708

Gnomad4 ASJ AF: 0.758

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.839

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.640

Alfa AF: 0.598 Hom.: 3527

Bravo AF: 0.567

Asia WGS AF: 0.634 AC: 2202 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.3
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs380092; hg19: chr2-113888900;