dbSNP rs2856837: IL1A:c.-9+95C>T (chr2-112784348-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001371554.1(IL1A):c.-42C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,430 control chromosomes in the GnomAD database, including 5,568 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.26 ( 5564 hom., cov: 33)

Exomes 𝑓: 0.22 ( 4 hom. )

Consequence

IL1A
NM_001371554.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.132

Publications

18 publications found

Variant links:

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]

IL1A links:

ENSG00000299339 (HGNC:):

ENSG00000299339 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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_001371554.1. 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.-9+95C>T		intron	N/A	NP_000566.3
	IL1A	NM_001371554.1		c.-42C>T		5_prime_UTR	Exon 1 of 7	NP_001358483.1	P01583

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL1A	ENST00000263339.4	TSL:1 MANE Select	c.-9+95C>T	intron	N/A	ENSP00000263339.3	P01583
IL1A	ENST00000959423.1		c.-578C>T	5_prime_UTR	Exon 1 of 6	ENSP00000629482.1
ENSG00000299339	ENST00000762706.1		n.404+13452G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40289

AN:

152080

Hom.:

5561

Cov.:

show subpopulations

Gnomad AFR

AF:

0.208

Gnomad AMI

AF:

0.409

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.0793

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.271

GnomAD4 exome

AF:

0.220

AC:

AN:

232

Hom.:

AF XY:

0.239

AC XY:

AN XY:

134

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AF:

0.375

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.233

AC:

AN:

176

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.534

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.265

AC:

40315

AN:

152198

Hom.:

5564

Cov.:

AF XY:

0.267

AC XY:

19869

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.208

AC:

8642

AN:

41540

American (AMR)

AF:

0.273

AC:

4170

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

1191

AN:

3472

East Asian (EAS)

AF:

0.0793

AC:

411

AN:

5186

South Asian (SAS)

AF:

0.298

AC:

1439

AN:

4828

European-Finnish (FIN)

AF:

0.316

AC:

3337

AN:

10566

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.295

AC:

20078

AN:

67992

Other (OTH)

AF:

0.270

AC:

570

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1572

3144

4716

6288

7860

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.283

Hom.:

17260

Bravo

AF:

0.255

Asia WGS

AF:

0.204

AC:

710

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

8.0

(source)

DANN

Benign

0.45

PhyloP100

-0.13

PromoterAI

-0.018

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over