chr2-112781669-C-T

Variant names:

• chr2-112781669-C-T
• rs3783531
• NM_000575.5:c.254G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000575.5(IL1A):​c.254G>A​(p.Arg85Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00234 in 1,614,206 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (7 hom.)
• Consequence: IL1A NM_000575.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.47
• Publications: 13 publications found

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]

ENSG00000299339 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02240938).
• BS2: High Homozygotes in GnomAdExome4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000575.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1A	NM_000575.5	MANE Select	c.254G>A	p.Arg85Gln	missense	Exon 4 of 7	NP_000566.3
	IL1A	NM_001371554.1		c.254G>A	p.Arg85Gln	missense	Exon 4 of 7	NP_001358483.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1A	ENST00000263339.4	TSL:1 MANE Select	c.254G>A	p.Arg85Gln	missense	Exon 4 of 7	ENSP00000263339.3
	ENSG00000299339	ENST00000762706.1		n.404+10773C>T		intron	N/A
	ENSG00000299339	ENST00000762707.1		n.499+10773C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00153 AC: 233 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00276

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00141 AC: 355 AN: 251464 AF XY: 0.00132

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000896

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00270

Gnomad OTH exome AF: 0.000977

GnomAD4 exome AF: 0.00242 AC: 3541 AN: 1461880 Hom.: 7 Cov.: 32 AF XY: 0.00236 AC XY: 1717 AN XY: 727238

African (AFR) AF: 0.000329 AC: 11 AN: 33480

American (AMR) AF: 0.000872 AC: 39 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.000393 AC: 21 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00304 AC: 3381 AN: 1112002

Other (OTH) AF: 0.00142 AC: 86 AN: 60396

GnomAD4 genome AF: 0.00153 AC: 233 AN: 152326 Hom.: 0 Cov.: 32 AF XY: 0.00141 AC XY: 105 AN XY: 74484

African (AFR) AF: 0.000577 AC: 24 AN: 41568

American (AMR) AF: 0.000980 AC: 15 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00276 AC: 188 AN: 68032

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00225 Hom.: 1

Bravo AF: 0.00147

TwinsUK AF: 0.00243 AC: 9

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00267 AC: 23

ExAC AF: 0.00145 AC: 176

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00289

EpiControl AF: 0.00249

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.067
FATHMM_MKL	Benign	0.19	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	2.0	M
PhyloP100		3.5
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.18
Sift	Benign	0.045	D
Sift4G	Uncertain	0.022	D
Polyphen		1.0	D
Vest4		0.32
MVP		0.86
MPC		0.83
ClinPred		0.020	T
GERP RS		4.9
Varity_R		0.18
gMVP		0.17
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs3783531; hg19: chr2-113539246;