X-28789325-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBP6_Very_Strong

The NM_014271.4(IL1RAPL1):c.-19G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 17099 hom., 20472 hem., cov: 23)

Exomes 𝑓: 0.52 ( 99590 hom. 169950 hem. )

Failed GnomAD Quality Control

Consequence

IL1RAPL1
NM_014271.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.755

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant X-28789325-G-A is Benign according to our data. Variant chrX-28789325-G-A is described in ClinVar as [Benign]. Clinvar id is 281021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-28789325-G-A is described in Lovd as [Benign]. Variant chrX-28789325-G-A is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RAPL1	NM_014271.4 link	c.-19G>A		5_prime_UTR_variant	Exon 2 of 11	ENST00000378993.6	NP_055086.1	Q9NZN1-1X5DNQ7
IL1RAPL1	XM_017029240.2 link	c.-19G>A		5_prime_UTR_variant	Exon 2 of 11		XP_016884729.1	Q9NZN1-1X5DNQ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RAPL1	ENST00000378993 link	c.-19G>A		5_prime_UTR_variant	Exon 2 of 11	1	NM_014271.4	ENSP00000368278.1		Q9NZN1-1

Frequencies

GnomAD3 genomes

AF:

0.632

AC:

69709

AN:

110355

Hom.:

17086

Cov.:

AF XY:

0.627

AC XY:

20430

AN XY:

32589

show subpopulations

Gnomad AFR

AF:

0.908

Gnomad AMI

AF:

0.341

Gnomad AMR

AF:

0.598

Gnomad ASJ

AF:

0.655

Gnomad EAS

AF:

0.847

Gnomad SAS

AF:

0.608

Gnomad FIN

AF:

0.458

Gnomad MID

AF:

0.685

Gnomad NFE

AF:

0.487

Gnomad OTH

AF:

0.629

GnomAD3 exomes

AF:

0.585

AC:

105986

AN:

181267

Hom.:

21364

AF XY:

0.574

AC XY:

37857

AN XY:

65911

show subpopulations

Gnomad AFR exome

AF:

0.916

Gnomad AMR exome

AF:

0.616

Gnomad ASJ exome

AF:

0.636

Gnomad EAS exome

AF:

0.838

Gnomad SAS exome

AF:

0.611

Gnomad FIN exome

AF:

0.461

Gnomad NFE exome

AF:

0.492

Gnomad OTH exome

AF:

0.571

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.524

AC:

539644

AN:

1028904

Hom.:

99590

Cov.:

AF XY:

0.538

AC XY:

169950

AN XY:

315748

show subpopulations

Gnomad4 AFR exome

AF:

0.922

Gnomad4 AMR exome

AF:

0.614

Gnomad4 ASJ exome

AF:

0.637

Gnomad4 EAS exome

AF:

0.822

Gnomad4 SAS exome

AF:

0.620

Gnomad4 FIN exome

AF:

0.450

Gnomad4 NFE exome

AF:

0.487

Gnomad4 OTH exome

AF:

0.574

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.632

AC:

69766

AN:

110401

Hom.:

17099

Cov.:

AF XY:

0.627

AC XY:

20472

AN XY:

32645

show subpopulations

Gnomad4 AFR

AF:

0.908

Gnomad4 AMR

AF:

0.599

Gnomad4 ASJ

AF:

0.655

Gnomad4 EAS

AF:

0.847

Gnomad4 SAS

AF:

0.609

Gnomad4 FIN

AF:

0.458

Gnomad4 NFE

AF:

0.487

Gnomad4 OTH

AF:

0.633

Alfa

AF:

0.534

Hom.:

28361

Bravo

AF:

0.660

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Aug 11, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Intellectual disability, X-linked 21

Benign:2

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This 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

-0.43

CADD

Benign

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over