rs7056388

Positions:

• chrX-29645910-A-G

Variant summary

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

The NM_014271.4(IL1RAPL1):​c.704-22520A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 111,785 control chromosomes in the GnomAD database, including 967 homozygotes. There are 3,987 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 0.13 (967 hom., 3987 hem., cov: 23)
• Consequence: IL1RAPL1 NM_014271.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.551

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RAPL1	NM_014271.4	c.704-22520A>G		intron_variant		ENST00000378993.6	NP_055086.1
IL1RAPL1	XM_017029240.2	c.704-22520A>G		intron_variant			XP_016884729.1
IL1RAPL1	XM_017029241.2	c.326-22520A>G		intron_variant			XP_016884730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RAPL1	ENST00000378993.6	c.704-22520A>G		intron_variant		1	NM_014271.4	ENSP00000368278.1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 14464 AN: 111729 Hom.: 969 Cov.: 23 AF XY: 0.117 AC XY: 3968 AN XY: 33947

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.0762

Gnomad AMR AF: 0.0920

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0733

Gnomad FIN AF: 0.0273

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.0894

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.130 AC: 14477 AN: 111785 Hom.: 967 Cov.: 23 AF XY: 0.117 AC XY: 3987 AN XY: 34013

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.0919

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0743

Gnomad4 FIN AF: 0.0273

Gnomad4 NFE AF: 0.0894

Gnomad4 OTH AF: 0.119

Alfa AF: 0.102 Hom.: 1795

Bravo AF: 0.139

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.70

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: rs7056388; hg19: chrX-29664027;