2-112779646-C-A

Variant names:

• chr2-112779646-C-A
• rs17561
• NM_000575.5:c.340G>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BA1

The NM_000575.5(IL1A):​c.340G>T​(p.Ala114Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,604,102 control chromosomes in the GnomAD database, including 67,974 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.26 (5330 hom., cov: 32)
  • Exomes 𝑓: 0.29 (62644 hom.)
• Consequence: IL1A NM_000575.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.83
• Publications: 288 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 -9 ACMG points.

• BP6: Variant 2-112779646-C-A is Benign according to our data. Variant chr2-112779646-C-A is described in ClinVar as Benign. ClinVar VariationId is 3060243.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1A	NM_000575.5	MANE Select	c.340G>T	p.Ala114Ser	missense	Exon 5 of 7	NP_000566.3
	IL1A	NM_001371554.1		c.340G>T	p.Ala114Ser	missense	Exon 5 of 7	NP_001358483.1	P01583

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1A	ENST00000263339.4	TSL:1 MANE Select	c.340G>T	p.Ala114Ser	missense	Exon 5 of 7	ENSP00000263339.3	P01583
	IL1A	ENST00000959423.1		c.340G>T	p.Ala114Ser	missense	Exon 4 of 6	ENSP00000629482.1
	ENSG00000299339	ENST00000762706.1		n.404+8750C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39015 AN: 151936 Hom.: 5326 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.0797

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.265

GnomAD2 exomes AF: 0.270 AC: 67603 AN: 250734 AF XY: 0.275

Gnomad AFR exome AF: 0.176

Gnomad AMR exome AF: 0.234

Gnomad ASJ exome AF: 0.340

Gnomad EAS exome AF: 0.0748

Gnomad FIN exome AF: 0.307

Gnomad NFE exome AF: 0.301

Gnomad OTH exome AF: 0.289

GnomAD4 exome AF: 0.290 AC: 421059 AN: 1452046 Hom.: 62644 Cov.: 32 AF XY: 0.291 AC XY: 210151 AN XY: 720964

African (AFR) AF: 0.177 AC: 5887 AN: 33328

American (AMR) AF: 0.237 AC: 10572 AN: 44566

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 8887 AN: 25954

East Asian (EAS) AF: 0.0896 AC: 3534 AN: 39446

South Asian (SAS) AF: 0.306 AC: 26292 AN: 85846

European-Finnish (FIN) AF: 0.315 AC: 16761 AN: 53246

Middle Eastern (MID) AF: 0.366 AC: 2099 AN: 5740

European-Non Finnish (NFE) AF: 0.299 AC: 329970 AN: 1103922

Other (OTH) AF: 0.284 AC: 17057 AN: 59998

GnomAD4 genome AF: 0.257 AC: 39041 AN: 152056 Hom.: 5330 Cov.: 32 AF XY: 0.259 AC XY: 19239 AN XY: 74292

African (AFR) AF: 0.180 AC: 7464 AN: 41480

American (AMR) AF: 0.270 AC: 4129 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1191 AN: 3472

East Asian (EAS) AF: 0.0797 AC: 413 AN: 5180

South Asian (SAS) AF: 0.298 AC: 1435 AN: 4816

European-Finnish (FIN) AF: 0.316 AC: 3327 AN: 10544

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20049 AN: 67970

Other (OTH) AF: 0.263 AC: 556 AN: 2112

Alfa AF: 0.279 Hom.: 20541

Bravo AF: 0.246

TwinsUK AF: 0.303 AC: 1122

ALSPAC AF: 0.301 AC: 1161

ESP6500AA AF: 0.183 AC: 808

ESP6500EA AF: 0.302 AC: 2595

ExAC AF: 0.272 AC: 33070

Asia WGS AF: 0.202 AC: 703 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	IL1A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.067
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.0056	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.8
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.081
Sift	Benign	0.20	T
Sift4G	Uncertain	0.043	D
Polyphen		0.98	D
Vest4		0.21
MPC		0.64
ClinPred		0.024	T
GERP RS		4.4
Varity_R		0.092
gMVP		0.17
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.39		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.39		Position offset: -11

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

Other links and lift over

dbSNP: rs17561; hg19: chr2-113537223; COSMIC: COSV54518892;