rs2006793

Variant names:

• chrX-29466736-G-A
• rs2006793
• NM_014271.4:c.703+67428G>A

Variant summary

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

The NM_014271.4(IL1RAPL1):​c.703+67428G>A 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 0.63 (16774 hom., 20442 hem., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: IL1RAPL1 NM_014271.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.450
• Publications: 1 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• non-syndromic X-linked intellectual disability

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

ENSG00000309436 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).

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.703+67428G>A		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.703+67428G>A		intron	N/A	ENSP00000368278.1	Q9NZN1-1
	ENSG00000309436	ENST00000841139.1		n.111-11731C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.627 AC: 69442 AN: 110700 Hom.: 16768 Cov.: 24

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.578

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: 0.628 AC: 69503 AN: 110752 Hom.: 16774 Cov.: 24 AF XY: 0.620 AC XY: 20442 AN XY: 32980

African (AFR) AF: 0.897 AC: 27400 AN: 30539

American (AMR) AF: 0.434 AC: 4530 AN: 10442

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1495 AN: 2628

East Asian (EAS) AF: 0.769 AC: 2673 AN: 3476

South Asian (SAS) AF: 0.717 AC: 1870 AN: 2609

European-Finnish (FIN) AF: 0.554 AC: 3222 AN: 5811

Middle Eastern (MID) AF: 0.477 AC: 102 AN: 214

European-Non Finnish (NFE) AF: 0.513 AC: 27127 AN: 52844

Other (OTH) AF: 0.583 AC: 882 AN: 1514

Alfa AF: 0.546 Hom.: 51841

Bravo AF: 0.628

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.7
DANN	Benign	0.70
PhyloP100		0.45
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2006793;

hg19: chrX-29484853;