NM_017416.2:c.773-8543G>T

Variant names:

• chrX-105708824-G-T
• rs6621992
• NM_017416.2:c.773-8543G>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.773-8543G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 110,745 control chromosomes in the GnomAD database, including 2,768 homozygotes. There are 7,647 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 0.22 (2768 hom., 7647 hem., cov: 23)
• Consequence: IL1RAPL2 NM_017416.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.37
• 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]

LOC105373303 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RAPL2	NM_017416.2	c.773-8543G>T		intron_variant	Intron 6 of 10	ENST00000372582.6	NP_059112.1
IL1RAPL2	XM_011530905.3	c.401-8543G>T		intron_variant	Intron 4 of 8		XP_011529207.1
LOC105373303	XR_007068300.1	n.890-1468C>A		intron_variant	Intron 4 of 4
LOC105373303	XR_938493.3	n.662+8450C>A		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RAPL2	ENST00000372582.6	c.773-8543G>T		intron_variant	Intron 6 of 10	1	NM_017416.2	ENSP00000361663.1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 24749 AN: 110693 Hom.: 2763 Cov.: 23

Gnomad AFR AF: 0.0396

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.0766

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.223 AC: 24750 AN: 110745 Hom.: 2768 Cov.: 23 AF XY: 0.231 AC XY: 7647 AN XY: 33075

African (AFR) AF: 0.0395 AC: 1214 AN: 30713

American (AMR) AF: 0.441 AC: 4576 AN: 10381

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 465 AN: 2628

East Asian (EAS) AF: 0.633 AC: 2168 AN: 3427

South Asian (SAS) AF: 0.282 AC: 760 AN: 2694

European-Finnish (FIN) AF: 0.371 AC: 2135 AN: 5747

Middle Eastern (MID) AF: 0.0791 AC: 17 AN: 215

European-Non Finnish (NFE) AF: 0.244 AC: 12892 AN: 52769

Other (OTH) AF: 0.245 AC: 366 AN: 1494

Alfa AF: 0.248 Hom.: 17777

Bravo AF: 0.230

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.5
DANN	Benign	0.45
PhyloP100		2.4
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: rs6621992; hg19: chrX-104952817;