rs4893595

chrX-28838401-G-AchrX-28838401-G-CchrX-28838401-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

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

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS2: High Homozygotes in GnomAd at 17110 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RAPL1	NM_014271.4	c.82+48976G>A		intron_variant		ENST00000378993.6
IL1RAPL1	XM_017029240.2	c.82+48976G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RAPL1	ENST00000378993.6	c.82+48976G>A		intron_variant		1	NM_014271.4	P1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 69279 AN: 109614 Hom.: 17110 Cov.: 22 AF XY: 0.625 AC XY: 20085 AN XY: 32122

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

Gnomad4 AFR AF: 0.910

Gnomad4 AMR AF: 0.590

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.865

Gnomad4 SAS AF: 0.663

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.640

Alfa AF: 0.538 Hom.: 14343

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4893595; hg19: chrX-28856518;