rs6630730

Positions:

• chrX-28690737-C-T

Variant summary

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

The NM_014271.4(IL1RAPL1):​c.-24-98583C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0625 in 110,933 control chromosomes in the GnomAD database, including 426 homozygotes. There are 2,005 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 0.062 (426 hom., 2005 hem., cov: 22)
• Consequence: IL1RAPL1 NM_014271.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.970

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 = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RAPL1	NM_014271.4	c.-24-98583C>T		intron_variant		ENST00000378993.6	NP_055086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RAPL1	ENST00000378993.6	c.-24-98583C>T		intron_variant		1	NM_014271.4	ENSP00000368278	P1

Frequencies

GnomAD3 genomes AF: 0.0624 AC: 6923 AN: 110886 Hom.: 427 Cov.: 22 AF XY: 0.0601 AC XY: 1994 AN XY: 33156

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0520

Gnomad ASJ AF: 0.0283

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.00833

Gnomad MID AF: 0.0171

Gnomad NFE AF: 0.00269

Gnomad OTH AF: 0.0566

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

GnomAD4 genome AF: 0.0625 AC: 6930 AN: 110933 Hom.: 426 Cov.: 22 AF XY: 0.0604 AC XY: 2005 AN XY: 33213

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.0518

Gnomad4 ASJ AF: 0.0283

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.0232

Gnomad4 FIN AF: 0.00833

Gnomad4 NFE AF: 0.00267

Gnomad4 OTH AF: 0.0552

Alfa AF: 0.0157 Hom.: 1004

Bravo AF: 0.0772

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.42
DANN	Benign	0.66

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: rs6630730; hg19: chrX-28708854;