rs721953

Positions:

• chrX-105554463-G-A

Variant summary

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

The ENST00000372582.6(IL1RAPL2):​c.772+70076G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 110,467 control chromosomes in the GnomAD database, including 8,832 homozygotes. There are 12,748 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 0.40 (8832 hom., 12748 hem., cov: 23)
• Consequence: IL1RAPL2 ENST00000372582.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RAPL2	NM_017416.2	c.772+70076G>A		intron_variant		ENST00000372582.6	NP_059112.1
IL1RAPL2	XM_011530905.3	c.400+70076G>A		intron_variant			XP_011529207.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RAPL2	ENST00000372582.6	c.772+70076G>A		intron_variant		1	NM_017416.2	ENSP00000361663	P1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 43771 AN: 110422 Hom.: 8822 Cov.: 23 AF XY: 0.388 AC XY: 12702 AN XY: 32730

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.0866

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.397 AC: 43827 AN: 110467 Hom.: 8832 Cov.: 23 AF XY: 0.389 AC XY: 12748 AN XY: 32785

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.359

Alfa AF: 0.244 Hom.: 15294

Bravo AF: 0.443

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.27
DANN	Benign	0.68

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: rs721953; hg19: chrX-104798456;