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GeneBe

3-190656067-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The ENST00000317757.8(IL1RAP):c.1524G>A(p.Pro508=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 1,537,132 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0096 ( 27 hom., cov: 32)
Exomes 𝑓: 0.00090 ( 20 hom. )

Consequence

IL1RAP
ENST00000317757.8 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0530
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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=-0.55).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-190656067-G-A is Benign according to our data. Variant chr3-190656067-G-A is described in ClinVar as [Benign]. Clinvar id is 712519.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=-0.053 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0096 (1461/152122) while in subpopulation AFR AF= 0.0337 (1399/41492). AF 95% confidence interval is 0.0322. There are 27 homozygotes in gnomad4. There are 672 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
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 27 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IL1RAPNM_001167931.2 linkuse as main transcriptc.1524G>A p.Pro508= synonymous_variant 12/12
IL1RAPNM_001364879.1 linkuse as main transcriptc.1524G>A p.Pro508= synonymous_variant 11/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL1RAPENST00000317757.8 linkuse as main transcriptc.1524G>A p.Pro508= synonymous_variant 12/121 Q9NPH3-5

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00962
AC:
1463
AN:
152004
Hom.:
27
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0338
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00288
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00861
GnomAD3 exomes
AF:
0.00215
AC:
306
AN:
142168
Hom.:
3
AF XY:
0.00139
AC XY:
106
AN XY:
76038
show subpopulations
Gnomad AFR exome
AF:
0.0345
Gnomad AMR exome
AF:
0.00151
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000440
Gnomad FIN exome
AF:
0.000144
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.000467
GnomAD4 exome
AF:
0.000897
AC:
1243
AN:
1385010
Hom.:
20
Cov.:
31
AF XY:
0.000770
AC XY:
526
AN XY:
683420
show subpopulations
Gnomad4 AFR exome
AF:
0.0323
Gnomad4 AMR exome
AF:
0.00151
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000631
Gnomad4 FIN exome
AF:
0.0000857
Gnomad4 NFE exome
AF:
0.0000287
Gnomad4 OTH exome
AF:
0.00223
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00960
AC:
1461
AN:
152122
Hom.:
27
Cov.:
32
AF XY:
0.00903
AC XY:
672
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.0337
Gnomad4 AMR
AF:
0.00282
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00852
Alfa
AF:
0.159
Hom.:
2356
Bravo
AF:
0.0109
Asia WGS
AF:
0.00173
AC:
6
AN:
3478

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 testingInvitaeMay 18, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
Cadd
Benign
6.4
Dann
Benign
0.74

Splicing

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: rs116127803; hg19: chr3-190373856; API