rs6526806

Variant names:

• chrX-28789325-G-A
• rs6526806
• NM_014271.4:c.-19G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-28789325-G-A
• chrX-28789325-G-C
• chrX-28789325-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BP6_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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.755
• Publications: 13 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 281021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RAPL1	ENST00000378993.6	c.-19G>A		5_prime_UTR_variant	Exon 2 of 11	1	NM_014271.4	ENSP00000368278.1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 69709 AN: 110355 Hom.: 17086 Cov.: 23

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

GnomAD2 exomes AF: 0.585 AC: 105986 AN: 181267 AF XY: 0.574

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 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.: 20 AF XY: 0.538 AC XY: 169950 AN XY: 315748

African (AFR) AF: 0.922 AC: 23336 AN: 25314

American (AMR) AF: 0.614 AC: 21467 AN: 34990

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 12083 AN: 18957

East Asian (EAS) AF: 0.822 AC: 24552 AN: 29886

South Asian (SAS) AF: 0.620 AC: 32592 AN: 52597

European-Finnish (FIN) AF: 0.450 AC: 18135 AN: 40304

Middle Eastern (MID) AF: 0.697 AC: 2747 AN: 3939

European-Non Finnish (NFE) AF: 0.487 AC: 379546 AN: 779031

Other (OTH) AF: 0.574 AC: 25186 AN: 43886

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.632 AC: 69766 AN: 110401 Hom.: 17099 Cov.: 23 AF XY: 0.627 AC XY: 20472 AN XY: 32645

African (AFR) AF: 0.908 AC: 27683 AN: 30478

American (AMR) AF: 0.599 AC: 6171 AN: 10305

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 1729 AN: 2639

East Asian (EAS) AF: 0.847 AC: 2976 AN: 3515

South Asian (SAS) AF: 0.609 AC: 1580 AN: 2593

European-Finnish (FIN) AF: 0.458 AC: 2639 AN: 5764

Middle Eastern (MID) AF: 0.690 AC: 147 AN: 213

European-Non Finnish (NFE) AF: 0.487 AC: 25659 AN: 52715

Other (OTH) AF: 0.633 AC: 952 AN: 1505

Alfa AF: 0.550 Hom.: 38641

Bravo AF: 0.660

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

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	12
DANN	Benign	0.78
PhyloP100		0.76
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6526806; hg19: chrX-28807442;