X-28838401-G-A

Variant names:

• chrX-28838401-G-A
• rs4893595
• NM_014271.4:c.82+48976G>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.82+48976G>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 (17122 hom., 20132 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: IL1RAPL1 NM_014271.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81
• Publications: 0 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=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RAPL1	NM_014271.4	c.82+48976G>A		intron_variant	Intron 2 of 10	ENST00000378993.6	NP_055086.1
IL1RAPL1	XM_017029240.2	c.82+48976G>A		intron_variant	Intron 2 of 10		XP_016884729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RAPL1	ENST00000378993.6	c.82+48976G>A		intron_variant	Intron 2 of 10	1	NM_014271.4	ENSP00000368278.1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 69279 AN: 109614 Hom.: 17110 Cov.: 22

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.695

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.636

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: 69342 AN: 109665 Hom.: 17122 Cov.: 22 AF XY: 0.626 AC XY: 20132 AN XY: 32183

African (AFR) AF: 0.910 AC: 27576 AN: 30291

American (AMR) AF: 0.590 AC: 6022 AN: 10215

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 1728 AN: 2612

East Asian (EAS) AF: 0.865 AC: 2963 AN: 3425

South Asian (SAS) AF: 0.663 AC: 1730 AN: 2610

European-Finnish (FIN) AF: 0.450 AC: 2610 AN: 5806

Middle Eastern (MID) AF: 0.703 AC: 149 AN: 212

European-Non Finnish (NFE) AF: 0.485 AC: 25378 AN: 52323

Other (OTH) AF: 0.640 AC: 957 AN: 1495

Alfa AF: 0.558 Hom.: 22223

Bravo AF: 0.661

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	13
DANN	Benign	0.79
PhyloP100		1.8
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: rs4893595; hg19: chrX-28856518;