chrX-29511131-A-C

Position:

• chrX-29511131-A-C

Variant summary

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

The NM_014271.4(IL1RAPL1):​c.703+111823A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 110,774 control chromosomes in the GnomAD database, including 8,541 homozygotes. There are 14,958 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 0.46 (8541 hom., 14958 hem., cov: 23)
• Consequence: IL1RAPL1 NM_014271.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RAPL1	NM_014271.4	c.703+111823A>C		intron_variant		ENST00000378993.6	NP_055086.1
IL1RAPL1	XM_017029240.2	c.703+111823A>C		intron_variant			XP_016884729.1
IL1RAPL1	XM_017029241.2	c.325+111823A>C		intron_variant			XP_016884730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RAPL1	ENST00000378993.6	c.703+111823A>C		intron_variant		1	NM_014271.4	ENSP00000368278.1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 51040 AN: 110721 Hom.: 8551 Cov.: 23 AF XY: 0.453 AC XY: 14930 AN XY: 32981

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.407

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.461 AC: 51057 AN: 110774 Hom.: 8541 Cov.: 23 AF XY: 0.453 AC XY: 14958 AN XY: 33044

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.698

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.446

Alfa AF: 0.342 Hom.: 2109

Bravo AF: 0.450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.67

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: rs727562; hg19: chrX-29529248;