rs225031

Variant names:

• chrX-29073042-C-T
• rs225031
• NM_014271.4:c.83-209896C>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.83-209896C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 110,757 control chromosomes in the GnomAD database, including 5,937 homozygotes. There are 11,366 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 0.34 (5937 hom., 11366 hem., cov: 23)
• Consequence: IL1RAPL1 NM_014271.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.391
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014271.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAPL1	NM_014271.4	MANE Select	c.83-209896C>T		intron	N/A	NP_055086.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAPL1	ENST00000378993.6	TSL:1 MANE Select	c.83-209896C>T		intron	N/A	ENSP00000368278.1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 38211 AN: 110706 Hom.: 5936 Cov.: 23

Gnomad AFR AF: 0.0956

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.345 AC: 38211 AN: 110757 Hom.: 5937 Cov.: 23 AF XY: 0.344 AC XY: 11366 AN XY: 32993

African (AFR) AF: 0.0955 AC: 2926 AN: 30639

American (AMR) AF: 0.288 AC: 2999 AN: 10402

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1137 AN: 2639

East Asian (EAS) AF: 0.172 AC: 599 AN: 3489

South Asian (SAS) AF: 0.281 AC: 739 AN: 2628

European-Finnish (FIN) AF: 0.576 AC: 3337 AN: 5792

Middle Eastern (MID) AF: 0.321 AC: 69 AN: 215

European-Non Finnish (NFE) AF: 0.482 AC: 25430 AN: 52790

Other (OTH) AF: 0.341 AC: 509 AN: 1492

Alfa AF: 0.426 Hom.: 3097

Bravo AF: 0.313

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.43
PhyloP100		0.39
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: rs225031; hg19: chrX-29091159;