chrX-28789354-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_014271.4(IL1RAPL1):​c.11C>T​(p.Pro4Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000937 in 1,205,768 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 40 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P4P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 0.000098 ( 0 hom. 40 hem. )

Consequence

IL1RAPL1
NM_014271.4 missense

Scores

1
2
14

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.16
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 -14 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.13727984).
BP6
Variant X-28789354-C-T is Benign according to our data. Variant chrX-28789354-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2056458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Hemizygotes in GnomAdExome4 at 40 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IL1RAPL1NM_014271.4 linkuse as main transcriptc.11C>T p.Pro4Leu missense_variant 2/11 ENST00000378993.6
IL1RAPL1XM_017029240.2 linkuse as main transcriptc.11C>T p.Pro4Leu missense_variant 2/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL1RAPL1ENST00000378993.6 linkuse as main transcriptc.11C>T p.Pro4Leu missense_variant 2/111 NM_014271.4 P1Q9NZN1-1

Frequencies

GnomAD3 genomes
AF:
0.0000537
AC:
6
AN:
111740
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
33930
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000955
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:
0.0000941
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000764
AC:
14
AN:
183259
Hom.:
0
AF XY:
0.000103
AC XY:
7
AN XY:
67735
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:
0.000159
Gnomad OTH exome
AF:
0.000221
GnomAD4 exome
AF:
0.0000978
AC:
107
AN:
1094028
Hom.:
0
Cov.:
28
AF XY:
0.000111
AC XY:
40
AN XY:
359668
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000284
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:
0.000124
Gnomad4 OTH exome
AF:
0.0000435
GnomAD4 genome
AF:
0.0000537
AC:
6
AN:
111740
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
33930
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000955
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000941
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000540
Hom.:
0
Bravo
AF:
0.0000340
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000346
AC:
1
ExAC
AF:
0.0000906
AC:
11
EpiCase
AF:
0.000218
EpiControl
AF:
0.000119

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2024IL1RAPL1: BS2 -
Benign, criteria provided, single submitterclinical testingInvitaeJul 20, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
19
DANN
Benign
0.41
DEOGEN2
Benign
0.16
T
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.74
T
M_CAP
Uncertain
0.14
D
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.22
N
MutationTaster
Benign
0.99
D;D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
0.19
N
REVEL
Benign
0.097
Sift
Benign
0.33
T
Sift4G
Benign
0.70
T
Polyphen
0.0020
B
Vest4
0.36
MVP
0.57
MPC
0.86
ClinPred
0.090
T
GERP RS
4.9
Varity_R
0.17
gMVP
0.55

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: rs773334103; hg19: chrX-28807471; API