rs6526833

Positions:

• chrX-29071792-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014271.4(IL1RAPL1):​c.83-211146G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 110,849 control chromosomes in the GnomAD database, including 2,551 homozygotes. There are 7,297 hemizygotes in GnomAD. 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 0.23 (2551 hom., 7297 hem., cov: 23)
• Consequence: IL1RAPL1 NM_014271.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RAPL1	NM_014271.4	c.83-211146G>A		intron_variant		ENST00000378993.6
IL1RAPL1	XM_017029240.2	c.83-211146G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RAPL1	ENST00000378993.6	c.83-211146G>A		intron_variant		1	NM_014271.4	P1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 25215 AN: 110798 Hom.: 2552 Cov.: 23 AF XY: 0.220 AC XY: 7289 AN XY: 33088

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.167

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.238

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.228 AC: 25220 AN: 110849 Hom.: 2551 Cov.: 23 AF XY: 0.220 AC XY: 7297 AN XY: 33149

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.237

Alfa AF: 0.159 Hom.: 11341

Bravo AF: 0.253

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.6
DANN	Benign	0.84

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: rs6526833; hg19: chrX-29089909;