rs225061

Variant names:

• chrX-29134105-A-C
• rs225061
• NM_014271.4:c.83-148833A>C

Your query was ambiguous. Multiple possible variants found:

• chrX-29134105-A-C
• chrX-29134105-A-G
• chrX-29134105-A-T

Variant summary

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

The NM_014271.4(IL1RAPL1):​c.83-148833A>C 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 0.86 (29052 hom., 28576 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: IL1RAPL1 NM_014271.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• Publications: 4 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: 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAPL1	NM_014271.4	MANE Select	c.83-148833A>C		intron	N/A	NP_055086.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAPL1	ENST00000378993.6	TSL:1 MANE Select	c.83-148833A>C		intron	N/A	ENSP00000368278.1

Frequencies

GnomAD3 genomes AF: 0.863 AC: 95483 AN: 110641 Hom.: 29053 Cov.: 23

Gnomad AFR AF: 0.969

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.941

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.852

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.850

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: 0.863 AC: 95538 AN: 110694 Hom.: 29052 Cov.: 23 AF XY: 0.868 AC XY: 28576 AN XY: 32928

African (AFR) AF: 0.969 AC: 29597 AN: 30533

American (AMR) AF: 0.838 AC: 8640 AN: 10314

Ashkenazi Jewish (ASJ) AF: 0.847 AC: 2230 AN: 2633

East Asian (EAS) AF: 0.887 AC: 3130 AN: 3527

South Asian (SAS) AF: 0.940 AC: 2451 AN: 2607

European-Finnish (FIN) AF: 0.850 AC: 4987 AN: 5868

Middle Eastern (MID) AF: 0.843 AC: 183 AN: 217

European-Non Finnish (NFE) AF: 0.805 AC: 42505 AN: 52822

Other (OTH) AF: 0.851 AC: 1272 AN: 1494

Alfa AF: 0.848 Hom.: 9094

Bravo AF: 0.866

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.3
DANN	Benign	0.68
PhyloP100		-0.055
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: rs225061; hg19: chrX-29152222;