NM_014271.4:c.-24-14774G>C

Variant names:

• chrX-28774546-G-C
• rs12847959
• NM_014271.4:c.-24-14774G>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.-24-14774G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 110,098 control chromosomes in the GnomAD database, including 8,116 homozygotes. There are 14,222 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 0.45 (8116 hom., 14222 hem., cov: 22)
• Consequence: IL1RAPL1 NM_014271.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RAPL1	NM_014271.4	c.-24-14774G>C		intron_variant	Intron 1 of 10	ENST00000378993.6	NP_055086.1
IL1RAPL1	XM_017029240.2	c.-24-14774G>C		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.-24-14774G>C		intron_variant	Intron 1 of 10	1	NM_014271.4	ENSP00000368278.1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 49231 AN: 110044 Hom.: 8105 Cov.: 22

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.447 AC: 49261 AN: 110098 Hom.: 8116 Cov.: 22 AF XY: 0.439 AC XY: 14222 AN XY: 32416

African (AFR) AF: 0.353 AC: 10703 AN: 30305

American (AMR) AF: 0.506 AC: 5184 AN: 10242

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 1652 AN: 2632

East Asian (EAS) AF: 0.445 AC: 1529 AN: 3436

South Asian (SAS) AF: 0.524 AC: 1349 AN: 2576

European-Finnish (FIN) AF: 0.451 AC: 2610 AN: 5787

Middle Eastern (MID) AF: 0.623 AC: 132 AN: 212

European-Non Finnish (NFE) AF: 0.478 AC: 25194 AN: 52740

Other (OTH) AF: 0.483 AC: 721 AN: 1493

Alfa AF: 0.190 Hom.: 726

Bravo AF: 0.452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.0
DANN	Benign	0.52
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12847959; hg19: chrX-28792663;