rs10218388

Variant names:

• chrX-105744956-T-C
• rs10218388
• NM_017416.2:c.1049-4004T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017416.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAPL2	NM_017416.2	MANE Select	c.1049-4004T>C		intron	N/A	NP_059112.1	Q9NP60

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAPL2	ENST00000372582.6	TSL:1 MANE Select	c.1049-4004T>C		intron	N/A	ENSP00000361663.1	Q9NP60
	IL1RAPL2	ENST00000485671.1	TSL:5	n.44-4004T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.137 AC: 15192 AN: 111167 Hom.: 873 Cov.: 22

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

African (AFR) AF: 0.218 AC: 6665 AN: 30506

American (AMR) AF: 0.0916 AC: 958 AN: 10457

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 399 AN: 2642

East Asian (EAS) AF: 0.224 AC: 774 AN: 3462

South Asian (SAS) AF: 0.256 AC: 666 AN: 2604

European-Finnish (FIN) AF: 0.0786 AC: 477 AN: 6070

Middle Eastern (MID) AF: 0.165 AC: 35 AN: 212

European-Non Finnish (NFE) AF: 0.0913 AC: 4845 AN: 53084

Other (OTH) AF: 0.129 AC: 194 AN: 1507

Alfa AF: 0.117 Hom.: 2060

Bravo AF: 0.143

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.1
DANN	Benign	0.71
PhyloP100		0.94
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10218388; hg19: chrX-104988949;