chrX-28789324-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.-20C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000999 in 1,133,249 control chromosomes in the GnomAD database, including 1 homozygotes. There are 353 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00078 ( 0 hom., 19 hem., cov: 23)
Exomes 𝑓: 0.0010 ( 1 hom. 334 hem. )

Consequence

IL1RAPL1
NM_014271.4 5_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.01
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 (BayesDel_noAF=-0.42).
BP6
Variant X-28789324-C-T is Benign according to our data. Variant chrX-28789324-C-T is described in ClinVar as [Benign]. Clinvar id is 368187.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Hemizygotes in GnomAd4 at 19 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IL1RAPL1NM_014271.4 linkuse as main transcriptc.-20C>T 5_prime_UTR_variant 2/11 ENST00000378993.6
IL1RAPL1XM_017029240.2 linkuse as main transcriptc.-20C>T 5_prime_UTR_variant 2/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL1RAPL1ENST00000378993.6 linkuse as main transcriptc.-20C>T 5_prime_UTR_variant 2/111 NM_014271.4 P1Q9NZN1-1

Frequencies

GnomAD3 genomes
AF:
0.000779
AC:
87
AN:
111641
Hom.:
0
Cov.:
23
AF XY:
0.000562
AC XY:
19
AN XY:
33809
show subpopulations
Gnomad AFR
AF:
0.0000976
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00210
Gnomad ASJ
AF:
0.000378
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00113
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00109
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000785
AC:
143
AN:
182217
Hom.:
0
AF XY:
0.000944
AC XY:
63
AN XY:
66769
show subpopulations
Gnomad AFR exome
AF:
0.000152
Gnomad AMR exome
AF:
0.000513
Gnomad ASJ exome
AF:
0.000538
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000960
Gnomad FIN exome
AF:
0.000126
Gnomad NFE exome
AF:
0.00118
Gnomad OTH exome
AF:
0.00156
GnomAD4 exome
AF:
0.00102
AC:
1045
AN:
1021564
Hom.:
1
Cov.:
19
AF XY:
0.00108
AC XY:
334
AN XY:
310192
show subpopulations
Gnomad4 AFR exome
AF:
0.000199
Gnomad4 AMR exome
AF:
0.000741
Gnomad4 ASJ exome
AF:
0.000476
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00118
Gnomad4 FIN exome
AF:
0.000124
Gnomad4 NFE exome
AF:
0.00113
Gnomad4 OTH exome
AF:
0.00108
GnomAD4 genome
AF:
0.000779
AC:
87
AN:
111685
Hom.:
0
Cov.:
23
AF XY:
0.000561
AC XY:
19
AN XY:
33863
show subpopulations
Gnomad4 AFR
AF:
0.0000974
Gnomad4 AMR
AF:
0.00210
Gnomad4 ASJ
AF:
0.000378
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00113
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00109
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00109
Hom.:
8
Bravo
AF:
0.00102

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMay 25, 2020- -
Intellectual disability, X-linked 21 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 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
-0.42
CADD
Benign
11
DANN
Benign
0.78

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: rs200878713; hg19: chrX-28807441; COSMIC: COSV100150718; API