rs6526807

Variant names:

• chrX-28789631-A-G
• rs6526807
• NM_014271.4:c.82+206A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_014271.4(IL1RAPL1):​c.82+206A>G variant causes a intron 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 (17139 hom., 20792 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: IL1RAPL1 NM_014271.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.259
• Publications: 3 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant X-28789631-A-G is Benign according to our data. Variant chrX-28789631-A-G is described in ClinVar as Benign. ClinVar VariationId is 1237882.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014271.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAPL1	NM_014271.4	MANE Select	c.82+206A>G		intron	N/A	NP_055086.1	X5DNQ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAPL1	ENST00000378993.6	TSL:1 MANE Select	c.82+206A>G		intron	N/A	ENSP00000368278.1	Q9NZN1-1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 70097 AN: 111003 Hom.: 17126 Cov.: 23

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.630

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: 0.632 AC: 70152 AN: 111048 Hom.: 17139 Cov.: 23 AF XY: 0.625 AC XY: 20792 AN XY: 33270

African (AFR) AF: 0.908 AC: 27761 AN: 30563

American (AMR) AF: 0.599 AC: 6243 AN: 10422

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 1723 AN: 2633

East Asian (EAS) AF: 0.846 AC: 2967 AN: 3506

South Asian (SAS) AF: 0.630 AC: 1679 AN: 2666

European-Finnish (FIN) AF: 0.456 AC: 2703 AN: 5926

Middle Eastern (MID) AF: 0.679 AC: 146 AN: 215

European-Non Finnish (NFE) AF: 0.486 AC: 25730 AN: 52912

Other (OTH) AF: 0.634 AC: 971 AN: 1532

Alfa AF: 0.571 Hom.: 6287

Bravo AF: 0.660

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.57
DANN	Benign	0.35
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6526807; hg19: chrX-28807748;