rs196990

chrX-28678286-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.-25+90239G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 110,154 control chromosomes in the GnomAD database, including 4,408 homozygotes. There are 10,111 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 0.32 (4408 hom., 10111 hem., cov: 22)
• Consequence: IL1RAPL1 NM_014271.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.360

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RAPL1	NM_014271.4	c.-25+90239G>A		intron_variant		ENST00000378993.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RAPL1	ENST00000378993.6	c.-25+90239G>A		intron_variant		1	NM_014271.4	P1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 35723 AN: 110099 Hom.: 4405 Cov.: 22 AF XY: 0.311 AC XY: 10079 AN XY: 32379

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.325 AC: 35763 AN: 110154 Hom.: 4408 Cov.: 22 AF XY: 0.312 AC XY: 10111 AN XY: 32444

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.351

Alfa AF: 0.328 Hom.: 28255

Bravo AF: 0.319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.86
Dann	Benign	0.93

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: rs196990; hg19: chrX-28696403; COSMIC: COSV66820273;