X-105554323-G-T

Variant names:

• chrX-105554323-G-T
• rs1384360
• NM_017416.2:c.772+69936G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017416.2(IL1RAPL2):​c.772+69936G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 110,979 control chromosomes in the GnomAD database, including 10,061 homozygotes. There are 14,801 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 0.45 (10061 hom., 14801 hem., cov: 24)
• Consequence: IL1RAPL2 NM_017416.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAPL2	NM_017416.2	MANE Select	c.772+69936G>T		intron	N/A	NP_059112.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAPL2	ENST00000372582.6	TSL:1 MANE Select	c.772+69936G>T		intron	N/A	ENSP00000361663.1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 49708 AN: 110932 Hom.: 10051 Cov.: 24

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.448 AC: 49765 AN: 110979 Hom.: 10061 Cov.: 24 AF XY: 0.444 AC XY: 14801 AN XY: 33353

African (AFR) AF: 0.777 AC: 23800 AN: 30630

American (AMR) AF: 0.536 AC: 5633 AN: 10508

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 609 AN: 2646

East Asian (EAS) AF: 0.683 AC: 2400 AN: 3515

South Asian (SAS) AF: 0.300 AC: 810 AN: 2704

European-Finnish (FIN) AF: 0.313 AC: 1816 AN: 5811

Middle Eastern (MID) AF: 0.162 AC: 34 AN: 210

European-Non Finnish (NFE) AF: 0.263 AC: 13861 AN: 52763

Other (OTH) AF: 0.412 AC: 626 AN: 1519

Alfa AF: 0.363 Hom.: 15659

Bravo AF: 0.488

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.021
DANN	Benign	0.12
PhyloP100		-1.4
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: rs1384360; hg19: chrX-104798316;