rs721953

Variant names:

• chrX-105554463-G-A
• rs721953
• NM_017416.2:c.772+70076G>A

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+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 NM_017416.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101
• Publications: 1 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=-0.79).
• 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 rank	MANE	Protein	UniProt
IL1RAPL2	NM_017416.2	c.772+70076G>A		intron_variant	Intron 6 of 10	ENST00000372582.6	NP_059112.1
IL1RAPL2	XM_011530905.3	c.400+70076G>A		intron_variant	Intron 4 of 8		XP_011529207.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RAPL2	ENST00000372582.6	c.772+70076G>A		intron_variant	Intron 6 of 10	1	NM_017416.2	ENSP00000361663.1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 43771 AN: 110422 Hom.: 8822 Cov.: 23

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

African (AFR) AF: 0.755 AC: 22919 AN: 30368

American (AMR) AF: 0.496 AC: 5166 AN: 10414

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 443 AN: 2626

East Asian (EAS) AF: 0.683 AC: 2375 AN: 3479

South Asian (SAS) AF: 0.235 AC: 622 AN: 2647

European-Finnish (FIN) AF: 0.253 AC: 1454 AN: 5753

Middle Eastern (MID) AF: 0.0948 AC: 20 AN: 211

European-Non Finnish (NFE) AF: 0.192 AC: 10138 AN: 52783

Other (OTH) AF: 0.359 AC: 542 AN: 1508

Alfa AF: 0.291 Hom.: 25603

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
PhyloP100		-0.10
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: rs721953; hg19: chrX-104798456;