2-112781647-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_000575.5(IL1A):c.276C>T(p.Ile92=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00339 in 1,614,176 control chromosomes in the GnomAD database, including 164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (75 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (89 hom.)
• Consequence: IL1A NM_000575.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00300

Genes affected

IL1A (HGNC:5991): (interleukin 1 alpha) The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine is a pleiotropic cytokine involved in various immune responses, inflammatory processes, and hematopoiesis. This cytokine is produced by monocytes and macrophages as a proprotein, which is proteolytically processed and released in response to cell injury, and thus induces apoptosis. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. It has been suggested that the polymorphism of these genes is associated with rheumatoid arthritis and Alzheimer's disease. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-112781647-G-A is Benign according to our data. Variant chr2-112781647-G-A is described in ClinVar as [Benign]. Clinvar id is 775754.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.003 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1A	NM_000575.5	c.276C>T	p.Ile92=	synonymous_variant	4/7	ENST00000263339.4
IL1A	NM_001371554.1	c.276C>T	p.Ile92=	synonymous_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1A	ENST00000263339.4	c.276C>T	p.Ile92=	synonymous_variant	4/7	1	NM_000575.5	P1

Frequencies

GnomAD3 genomes AF: 0.0184 AC: 2801 AN: 152180 Hom.: 73 Cov.: 32

Gnomad AFR AF: 0.0640

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00726

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0139

GnomAD3 exomes AF: 0.00459 AC: 1155 AN: 251480 Hom.: 30 AF XY: 0.00324 AC XY: 441 AN XY: 135914

Gnomad AFR exome AF: 0.0640

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00181 AC: 2649 AN: 1461878 Hom.: 89 Cov.: 32 AF XY: 0.00157 AC XY: 1140 AN XY: 727240

Gnomad4 AFR exome AF: 0.0664

Gnomad4 AMR exome AF: 0.00304

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000522

Gnomad4 OTH exome AF: 0.00364

GnomAD4 genome AF: 0.0185 AC: 2823 AN: 152298 Hom.: 75 Cov.: 32 AF XY: 0.0171 AC XY: 1277 AN XY: 74482

Gnomad4 AFR AF: 0.0643

Gnomad4 AMR AF: 0.00725

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.0138

Alfa AF: 0.00859 Hom.: 22

Bravo AF: 0.0210

Asia WGS AF: 0.00375 AC: 14 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 24, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.0
Dann	Benign	0.71

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: rs20540; hg19: chr2-113539224; COSMIC: COSV54520237;