rs10218388

Positions:

• chrX-105744956-T-C

Variant summary

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

The NM_017416.2(IL1RAPL2):​c.1049-4004T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 111,223 control chromosomes in the GnomAD database, including 869 homozygotes. There are 4,394 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 0.14 (869 hom., 4394 hem., cov: 22)
• Consequence: IL1RAPL2 NM_017416.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.935

Genes affected

IL1RAPL2 (HGNC:5997): (interleukin 1 receptor accessory protein like 2) The protein encoded by this gene is a member of the interleukin 1 receptor family. This protein is similar to the interleukin 1 accessory proteins, and is most closely related to interleukin 1 receptor accessory protein-like 1 (IL1RAPL1). This gene and IL1RAPL1 are located at a region on chromosome X that is associated with X-linked non-syndromic cognitive disability. [provided by RefSeq, Jul 2008]

LOC105373303 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RAPL2	NM_017416.2	c.1049-4004T>C		intron_variant		ENST00000372582.6	NP_059112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RAPL2	ENST00000372582.6	c.1049-4004T>C		intron_variant		1	NM_017416.2	ENSP00000361663.1
IL1RAPL2	ENST00000485671.1	n.44-4004T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.137 AC: 15192 AN: 111167 Hom.: 873 Cov.: 22 AF XY: 0.131 AC XY: 4386 AN XY: 33373

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.0916

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.0786

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.0912

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.137 AC: 15195 AN: 111223 Hom.: 869 Cov.: 22 AF XY: 0.131 AC XY: 4394 AN XY: 33439

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.0916

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.0786

Gnomad4 NFE AF: 0.0913

Gnomad4 OTH AF: 0.129

Alfa AF: 0.110 Hom.: 1136

Bravo AF: 0.143

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.1
DANN	Benign	0.71

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: rs10218388; hg19: chrX-104988949;