Genetic Variant IL1RAPL1:c.-24-9096T>C (chrX-28780224-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014271.4(IL1RAPL1):c.-24-9096T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.64 ( 17359 hom., 19706 hem., cov: 21)

Failed GnomAD Quality Control

Consequence

IL1RAPL1
NM_014271.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.80

Publications

1 publications found

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]

IL1RAPL1 Gene-Disease associations (from GenCC):

intellectual disability, X-linked 21
Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
non-syndromic X-linked intellectual disability
Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen

IL1RAPL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RAPL1	NM_014271.4 link	c.-24-9096T>C		intron_variant	Intron 1 of 10	ENST00000378993.6	NP_055086.1	Q9NZN1-1X5DNQ7
IL1RAPL1	XM_017029240.2 link	c.-24-9096T>C		intron_variant	Intron 1 of 10		XP_016884729.1	Q9NZN1-1X5DNQ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RAPL1	ENST00000378993.6 link	c.-24-9096T>C		intron_variant	Intron 1 of 10	1	NM_014271.4	ENSP00000368278.1		Q9NZN1-1

Frequencies

GnomAD3 genomes

AF:

0.636

AC:

69410

AN:

109081

Hom.:

17346

Cov.:

show subpopulations

Gnomad AFR

AF:

0.908

Gnomad AMI

AF:

0.338

Gnomad AMR

AF:

0.602

Gnomad ASJ

AF:

0.670

Gnomad EAS

AF:

0.849

Gnomad SAS

AF:

0.622

Gnomad FIN

AF:

0.474

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.493

Gnomad OTH

AF:

0.640

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.637

AC:

69475

AN:

109132

Hom.:

17359

Cov.:

AF XY:

0.625

AC XY:

19706

AN XY:

31542

show subpopulations

African (AFR)

AF:

0.908

AC:

27307

AN:

30081

American (AMR)

AF:

0.603

AC:

6139

AN:

10185

Ashkenazi Jewish (ASJ)

AF:

0.670

AC:

1746

AN:

2606

East Asian (EAS)

AF:

0.848

AC:

2924

AN:

3449

South Asian (SAS)

AF:

0.623

AC:

1586

AN:

2547

European-Finnish (FIN)

AF:

0.474

AC:

2701

AN:

5702

Middle Eastern (MID)

AF:

0.687

AC:

147

AN:

214

European-Non Finnish (NFE)

AF:

0.493

AC:

25732

AN:

52173

Other (OTH)

AF:

0.644

AC:

964

AN:

1497

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

766

1532

2297

3063

3829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

598

1196

1794

2392

2990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.565

Hom.:

5313

Bravo

AF:

0.665

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.38

(source)

DANN

Benign

0.70

PhyloP100

-1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over