rs12387961

Variant names:

• chrX-28712213-G-T
• rs12387961
• NM_014271.4:c.-24-77107G>T

Variant summary

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

The NM_014271.4(IL1RAPL1):​c.-24-77107G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 110,460 control chromosomes in the GnomAD database, including 2,746 homozygotes. There are 7,688 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 0.24 (2746 hom., 7688 hem., cov: 22)
• Consequence: IL1RAPL1 NM_014271.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RAPL1	NM_014271.4	c.-24-77107G>T		intron_variant	Intron 1 of 10	ENST00000378993.6	NP_055086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RAPL1	ENST00000378993.6	c.-24-77107G>T		intron_variant	Intron 1 of 10	1	NM_014271.4	ENSP00000368278.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 26884 AN: 110412 Hom.: 2741 Cov.: 22

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.407

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.243 AC: 26894 AN: 110460 Hom.: 2746 Cov.: 22 AF XY: 0.235 AC XY: 7688 AN XY: 32704

African (AFR) AF: 0.115 AC: 3502 AN: 30463

American (AMR) AF: 0.215 AC: 2224 AN: 10354

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 941 AN: 2631

East Asian (EAS) AF: 0.155 AC: 541 AN: 3490

South Asian (SAS) AF: 0.348 AC: 907 AN: 2605

European-Finnish (FIN) AF: 0.291 AC: 1690 AN: 5802

Middle Eastern (MID) AF: 0.410 AC: 86 AN: 210

European-Non Finnish (NFE) AF: 0.311 AC: 16397 AN: 52746

Other (OTH) AF: 0.290 AC: 432 AN: 1491

Alfa AF: 0.278 Hom.: 2243

Bravo AF: 0.230

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.0
DANN	Benign	0.41
PhyloP100		0.61
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: rs12387961; hg19: chrX-28730330;