chrX-28789355-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_014271.4(IL1RAPL1):​c.12G>A​(p.Pro4=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,206,504 control chromosomes in the GnomAD database, including 6 homozygotes. There are 587 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., 39 hem., cov: 23)
Exomes 𝑓: 0.0014 ( 5 hom. 548 hem. )

Consequence

IL1RAPL1
NM_014271.4 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.146
Variant links:
Genes affected
IL1RAPL1 (HGNC:5996): (interleukin 1 receptor accessory protein like 1) The protein encoded by this gene is a member of the interleukin 1 receptor family and is similar to the interleukin 1 accessory proteins. This protein has an N-terminal signal peptide, three extracellular immunoglobulin Ig-like domains, a transmembrane domain, an intracellular Toll/IL-1R domain, and a long C-terminal tail which interacts with multiple signalling molecules. This gene is located at a region on chromosome X that is associated with a non-syndromic form of X-linked intellectual disability. Deletions and mutations in this gene were found in patients with intellectual disability. This gene is expressed at a high level in post-natal brain structures involved in the hippocampal memory system, which suggests a specialized role in the physiological processes underlying memory and learning abilities, and plays a role in synapse formation and stabilization. [provided by RefSeq, Jul 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant X-28789355-G-A is Benign according to our data. Variant chrX-28789355-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 368188.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.146 with no splicing effect.
BS2
High Hemizygotes in GnomAd4 at 39 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IL1RAPL1NM_014271.4 linkuse as main transcriptc.12G>A p.Pro4= synonymous_variant 2/11 ENST00000378993.6
IL1RAPL1XM_017029240.2 linkuse as main transcriptc.12G>A p.Pro4= synonymous_variant 2/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL1RAPL1ENST00000378993.6 linkuse as main transcriptc.12G>A p.Pro4= synonymous_variant 2/111 NM_014271.4 P1Q9NZN1-1

Frequencies

GnomAD3 genomes
AF:
0.00125
AC:
140
AN:
111847
Hom.:
1
Cov.:
23
AF XY:
0.00115
AC XY:
39
AN XY:
34023
show subpopulations
Gnomad AFR
AF:
0.0000649
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000953
Gnomad ASJ
AF:
0.0242
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000370
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00844
Gnomad NFE
AF:
0.00130
Gnomad OTH
AF:
0.000662
GnomAD3 exomes
AF:
0.00152
AC:
278
AN:
183256
Hom.:
2
AF XY:
0.00165
AC XY:
112
AN XY:
67730
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000730
Gnomad ASJ exome
AF:
0.0199
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00184
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00103
Gnomad OTH exome
AF:
0.00177
GnomAD4 exome
AF:
0.00141
AC:
1547
AN:
1094604
Hom.:
5
Cov.:
28
AF XY:
0.00152
AC XY:
548
AN XY:
360198
show subpopulations
Gnomad4 AFR exome
AF:
0.0000380
Gnomad4 AMR exome
AF:
0.000142
Gnomad4 ASJ exome
AF:
0.0216
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00196
Gnomad4 FIN exome
AF:
0.0000247
Gnomad4 NFE exome
AF:
0.00108
Gnomad4 OTH exome
AF:
0.00231
GnomAD4 genome
AF:
0.00125
AC:
140
AN:
111900
Hom.:
1
Cov.:
23
AF XY:
0.00114
AC XY:
39
AN XY:
34086
show subpopulations
Gnomad4 AFR
AF:
0.0000648
Gnomad4 AMR
AF:
0.0000952
Gnomad4 ASJ
AF:
0.0242
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000371
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00130
Gnomad4 OTH
AF:
0.000654
Alfa
AF:
0.00324
Hom.:
26
Bravo
AF:
0.00124
EpiCase
AF:
0.00109
EpiControl
AF:
0.00172

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingInvitaeDec 21, 2023- -
Benign, criteria provided, single submitterclinical testingGeneDxSep 18, 2019- -
History of neurodevelopmental disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsAug 28, 2012This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Intellectual disability, X-linked 21 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.52
CADD
Benign
5.1
DANN
Benign
0.75

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: rs143600441; hg19: chrX-28807472; COSMIC: COSV56241025; API