chrX-28789402-A-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2

The NM_014271.4(IL1RAPL1):ā€‹c.59A>Gā€‹(p.Lys20Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000564 in 1,205,692 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.000045 ( 0 hom., 2 hem., cov: 23)
Exomes š‘“: 0.000058 ( 0 hom. 19 hem. )

Consequence

IL1RAPL1
NM_014271.4 missense

Scores

1
2
14

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.79
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 -7 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.34103692).
BP6
Variant X-28789402-A-G is Benign according to our data. Variant chrX-28789402-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3067362.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IL1RAPL1NM_014271.4 linkuse as main transcriptc.59A>G p.Lys20Arg missense_variant 2/11 ENST00000378993.6
IL1RAPL1XM_017029240.2 linkuse as main transcriptc.59A>G p.Lys20Arg missense_variant 2/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL1RAPL1ENST00000378993.6 linkuse as main transcriptc.59A>G p.Lys20Arg missense_variant 2/111 NM_014271.4 P1Q9NZN1-1

Frequencies

GnomAD3 genomes
AF:
0.0000446
AC:
5
AN:
112150
Hom.:
0
Cov.:
23
AF XY:
0.0000583
AC XY:
2
AN XY:
34302
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000939
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000982
AC:
18
AN:
183376
Hom.:
0
AF XY:
0.0000590
AC XY:
4
AN XY:
67842
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000220
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000576
AC:
63
AN:
1093542
Hom.:
0
Cov.:
28
AF XY:
0.0000529
AC XY:
19
AN XY:
359062
show subpopulations
Gnomad4 AFR exome
AF:
0.0000380
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000716
Gnomad4 OTH exome
AF:
0.0000435
GnomAD4 genome
AF:
0.0000446
AC:
5
AN:
112150
Hom.:
0
Cov.:
23
AF XY:
0.0000583
AC XY:
2
AN XY:
34302
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000939
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000604
ExAC
AF:
0.000123
AC:
15
EpiCase
AF:
0.000109
EpiControl
AF:
0.000237

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMar 01, 2024IL1RAPL1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.28
T
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.52
T
M_CAP
Benign
0.051
D
MetaRNN
Benign
0.34
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
M
MutationTaster
Benign
0.54
N;N
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-0.55
N
REVEL
Benign
0.23
Sift
Benign
0.32
T
Sift4G
Benign
0.27
T
Polyphen
0.0020
B
Vest4
0.55
MutPred
0.48
Loss of methylation at K20 (P = 0.0231);
MVP
0.95
MPC
0.70
ClinPred
0.20
T
GERP RS
5.8
Varity_R
0.20
gMVP
0.50

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: rs781634327; hg19: chrX-28807519; API