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GeneBe

3-190629458-C-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_002182.4(IL1RAP):c.1011C>A(p.Ala337=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00654 in 1,613,388 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 9 hom., cov: 32)
Exomes 𝑓: 0.0066 ( 44 hom. )

Consequence

IL1RAP
NM_002182.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.03
Variant links:
Genes affected
IL1RAP (HGNC:5995): (interleukin 1 receptor accessory protein) This gene encodes a component of the interleukin 1 receptor complex, which initiates signalling events that result in the activation of interleukin 1-responsive genes. Alternative splicing of this gene results in membrane-bound and soluble isoforms differing in their C-terminus. The ratio of soluble to membrane-bound forms increases during acute-phase induction or stress. [provided by RefSeq, Jul 2018]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.27).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-190629458-C-A is Benign according to our data. Variant chr3-190629458-C-A is described in ClinVar as [Benign]. Clinvar id is 790445.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.03 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IL1RAPNM_002182.4 linkuse as main transcriptc.1011C>A p.Ala337= synonymous_variant 9/12 ENST00000447382.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL1RAPENST00000447382.6 linkuse as main transcriptc.1011C>A p.Ala337= synonymous_variant 9/121 NM_002182.4 P1Q9NPH3-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00586
AC:
891
AN:
152166
Hom.:
9
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00123
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00347
Gnomad ASJ
AF:
0.00519
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00269
Gnomad FIN
AF:
0.0222
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00744
Gnomad OTH
AF:
0.00669
GnomAD3 exomes
AF:
0.00612
AC:
1532
AN:
250466
Hom.:
11
AF XY:
0.00637
AC XY:
862
AN XY:
135406
show subpopulations
Gnomad AFR exome
AF:
0.00123
Gnomad AMR exome
AF:
0.00105
Gnomad ASJ exome
AF:
0.00597
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00328
Gnomad FIN exome
AF:
0.0218
Gnomad NFE exome
AF:
0.00708
Gnomad OTH exome
AF:
0.00703
GnomAD4 exome
AF:
0.00661
AC:
9661
AN:
1461104
Hom.:
44
Cov.:
30
AF XY:
0.00661
AC XY:
4804
AN XY:
726862
show subpopulations
Gnomad4 AFR exome
AF:
0.000568
Gnomad4 AMR exome
AF:
0.00128
Gnomad4 ASJ exome
AF:
0.00594
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00328
Gnomad4 FIN exome
AF:
0.0216
Gnomad4 NFE exome
AF:
0.00685
Gnomad4 OTH exome
AF:
0.00548
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00585
AC:
891
AN:
152284
Hom.:
9
Cov.:
32
AF XY:
0.00608
AC XY:
453
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.00123
Gnomad4 AMR
AF:
0.00346
Gnomad4 ASJ
AF:
0.00519
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00269
Gnomad4 FIN
AF:
0.0222
Gnomad4 NFE
AF:
0.00744
Gnomad4 OTH
AF:
0.00662
Alfa
AF:
0.00774
Hom.:
4
Bravo
AF:
0.00434
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.00726
EpiControl
AF:
0.00654

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeApr 23, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.27
Cadd
Benign
9.5
Dann
Benign
0.74

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

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

Other links and lift over

dbSNP: rs148996090; hg19: chr3-190347247; API