NM_014271.4:c.-24-36752G>A

Variant names:

• chrX-28752568-G-A
• rs10521946
• NM_014271.4:c.-24-36752G>A

Variant summary

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

The NM_014271.4(IL1RAPL1):​c.-24-36752G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 111,619 control chromosomes in the GnomAD database, including 2,095 homozygotes. There are 6,881 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 (2095 hom., 6881 hem., cov: 23)
• Consequence: IL1RAPL1 NM_014271.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414
• 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RAPL1	NM_014271.4	c.-24-36752G>A		intron_variant	Intron 1 of 10	ENST00000378993.6	NP_055086.1
IL1RAPL1	XM_017029240.2	c.-25+34021G>A		intron_variant	Intron 1 of 10		XP_016884729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RAPL1	ENST00000378993.6	c.-24-36752G>A		intron_variant	Intron 1 of 10	1	NM_014271.4	ENSP00000368278.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 24187 AN: 111565 Hom.: 2094 Cov.: 23

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.0227

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.391

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.217 AC: 24211 AN: 111619 Hom.: 2095 Cov.: 23 AF XY: 0.203 AC XY: 6881 AN XY: 33861

African (AFR) AF: 0.277 AC: 8491 AN: 30630

American (AMR) AF: 0.144 AC: 1519 AN: 10532

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 770 AN: 2640

East Asian (EAS) AF: 0.0225 AC: 80 AN: 3555

South Asian (SAS) AF: 0.251 AC: 675 AN: 2686

European-Finnish (FIN) AF: 0.191 AC: 1151 AN: 6040

Middle Eastern (MID) AF: 0.388 AC: 83 AN: 214

European-Non Finnish (NFE) AF: 0.206 AC: 10935 AN: 53121

Other (OTH) AF: 0.231 AC: 352 AN: 1526

Alfa AF: 0.213 Hom.: 22451

Bravo AF: 0.214

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.9
DANN	Benign	0.49
PhyloP100		0.41
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: rs10521946; hg19: chrX-28770685;