rs10521947

Variant names:

• chrX-28839776-G-C
• rs10521947
• NM_014271.4:c.82+50351G>C

Variant summary

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

The NM_014271.4(IL1RAPL1):​c.82+50351G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 110,134 control chromosomes in the GnomAD database, including 1,869 homozygotes. There are 4,221 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 (1869 hom., 4221 hem., cov: 22)
• Consequence: IL1RAPL1 NM_014271.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.836
• Publications: 1 publications found

Genes affected

IL1RAPL1 (HGNC:5996): (interleukin 1 receptor accessory protein like 1) The protein encoded by this gene is a member of the interleukin 1 receptor family and is similar to the interleukin 1 accessory proteins. This protein has an N-terminal signal peptide, three extracellular immunoglobulin Ig-like domains, a transmembrane domain, an intracellular Toll/IL-1R domain, and a long C-terminal tail which interacts with multiple signalling molecules. This gene is located at a region on chromosome X that is associated with a non-syndromic form of X-linked intellectual disability. Deletions and mutations in this gene were found in patients with intellectual disability. This gene is expressed at a high level in post-natal brain structures involved in the hippocampal memory system, which suggests a specialized role in the physiological processes underlying memory and learning abilities, and plays a role in synapse formation and stabilization. [provided by RefSeq, Jul 2017]

IL1RAPL1 Gene-Disease associations (from GenCC):

• intellectual disability, X-linked 21

  Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen

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 = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RAPL1	NM_014271.4	c.82+50351G>C		intron_variant	Intron 2 of 10	ENST00000378993.6	NP_055086.1
IL1RAPL1	XM_017029240.2	c.82+50351G>C		intron_variant	Intron 2 of 10		XP_016884729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RAPL1	ENST00000378993.6	c.82+50351G>C		intron_variant	Intron 2 of 10	1	NM_014271.4	ENSP00000368278.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 15138 AN: 110079 Hom.: 1871 Cov.: 22

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.0563

Gnomad AMR AF: 0.0801

Gnomad ASJ AF: 0.0498

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0191

Gnomad MID AF: 0.0593

Gnomad NFE AF: 0.0138

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.138 AC: 15147 AN: 110134 Hom.: 1869 Cov.: 22 AF XY: 0.129 AC XY: 4221 AN XY: 32772

African (AFR) AF: 0.388 AC: 11748 AN: 30253

American (AMR) AF: 0.0797 AC: 824 AN: 10336

Ashkenazi Jewish (ASJ) AF: 0.0498 AC: 130 AN: 2613

East Asian (EAS) AF: 0.310 AC: 1073 AN: 3460

South Asian (SAS) AF: 0.113 AC: 304 AN: 2681

European-Finnish (FIN) AF: 0.0191 AC: 114 AN: 5966

Middle Eastern (MID) AF: 0.0602 AC: 13 AN: 216

European-Non Finnish (NFE) AF: 0.0138 AC: 723 AN: 52439

Other (OTH) AF: 0.120 AC: 180 AN: 1495

Alfa AF: 0.0805 Hom.: 449

Bravo AF: 0.158

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.46
DANN	Benign	0.43
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10521947; hg19: chrX-28857893;