dbSNP rs196990: IL1RAPL1:c.-25+90239G>A (chrX-28678286-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014271.4(IL1RAPL1):c.-25+90239G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 110,154 control chromosomes in the GnomAD database, including 4,408 homozygotes. There are 10,111 hemizygotes in GnomAD. 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 0.32 ( 4408 hom., 10111 hem., cov: 22)

Consequence

IL1RAPL1
NM_014271.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.360

Publications

2 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RAPL1	NM_014271.4 link	c.-25+90239G>A		intron_variant	Intron 1 of 10	ENST00000378993.6	NP_055086.1	Q9NZN1-1X5DNQ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RAPL1	ENST00000378993.6 link	c.-25+90239G>A		intron_variant	Intron 1 of 10	1	NM_014271.4	ENSP00000368278.1		Q9NZN1-1

Frequencies

GnomAD3 genomes

AF:

0.324

AC:

35723

AN:

110099

Hom.:

4405

Cov.:

show subpopulations

Gnomad AFR

AF:

0.353

Gnomad AMI

AF:

0.383

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.398

Gnomad EAS

AF:

0.157

Gnomad SAS

AF:

0.366

Gnomad FIN

AF:

0.298

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.328

Gnomad OTH

AF:

0.343

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

GnomAD4 genome

AF:

0.325

AC:

35763

AN:

110154

Hom.:

4408

Cov.:

AF XY:

0.312

AC XY:

10111

AN XY:

32444

show subpopulations

African (AFR)

AF:

0.354

AC:

10699

AN:

30248

American (AMR)

AF:

0.255

AC:

2626

AN:

10314

Ashkenazi Jewish (ASJ)

AF:

0.398

AC:

1049

AN:

2633

East Asian (EAS)

AF:

0.157

AC:

542

AN:

3462

South Asian (SAS)

AF:

0.367

AC:

943

AN:

2570

European-Finnish (FIN)

AF:

0.298

AC:

1722

AN:

5772

Middle Eastern (MID)

AF:

0.449

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.328

AC:

17299

AN:

52762

Other (OTH)

AF:

0.351

AC:

529

AN:

1506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

888

1775

2663

3550

4438

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

370

740

1110

1480

1850

<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:

0.330

Hom.:

37971

Bravo

AF:

0.319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.86

(source)

DANN

Benign

0.93

PhyloP100

0.36

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