Variant rs17561 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

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. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.26 ( 5330 hom., cov: 32)

Exomes 𝑓: 0.29 ( 62644 hom. )

Consequence

IL1A
NM_000575.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.83

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1A	NM_000575.5 linkuse as main transcript	c.340G>T	p.Ala114Ser	missense_variant	5/7	ENST00000263339.4	NP_000566.3
IL1A	NM_001371554.1 linkuse as main transcript	c.340G>T	p.Ala114Ser	missense_variant	5/7		NP_001358483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1A	ENST00000263339.4 linkuse as main transcript	c.340G>T	p.Ala114Ser	missense_variant	5/7	1	NM_000575.5	ENSP00000263339	P1

Frequencies

GnomAD3 genomes

AF:

0.257

AC:

39015

AN:

151936

Hom.:

5326

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.270

AC:

67603

AN:

250734

Hom.:

9650

AF XY:

0.275

AC XY:

37261

AN XY:

135534

show subpopulations

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 SAS exome

AF:

0.308

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.:

AF XY:

0.291

AC XY:

210151

AN XY:

720964

show subpopulations

Gnomad4 AFR exome

AF:

0.177

Gnomad4 AMR exome

AF:

0.237

Gnomad4 ASJ exome

AF:

0.342

Gnomad4 EAS exome

AF:

0.0896

Gnomad4 SAS exome

AF:

0.306

Gnomad4 FIN exome

AF:

0.315

Gnomad4 NFE exome

AF:

0.299

Gnomad4 OTH exome

AF:

0.284

GnomAD4 genome

AF:

0.257

AC:

39041

AN:

152056

Hom.:

5330

Cov.:

AF XY:

0.259

AC XY:

19239

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.180

Gnomad4 AMR

AF:

0.270

Gnomad4 ASJ

AF:

0.343

Gnomad4 EAS

AF:

0.0797

Gnomad4 SAS

AF:

0.298

Gnomad4 FIN

AF:

0.316

Gnomad4 NFE

AF:

0.295

Gnomad4 OTH

AF:

0.263

Alfa

AF:

0.285

Hom.:

15188

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

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

IL1A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 22, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

Eigen

Benign

-0.067

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0056

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.2

REVEL

Benign

0.081

Sift

Benign

0.20

Sift4G

Uncertain

0.043

Polyphen

0.98

Vest4

0.21

MPC

0.64

ClinPred

0.024

GERP RS

4.4

Varity_R

0.092

gMVP

0.17

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over