X-28855378-C-T

Variant names:

• chrX-28855378-C-T
• rs1318832
• NM_014271.4:c.82+65953C>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.82+65953C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 108,574 control chromosomes in the GnomAD database, including 12,379 homozygotes. There are 15,821 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 0.52 (12379 hom., 15821 hem., cov: 21)
• Consequence: IL1RAPL1 NM_014271.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• 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: ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.816 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAPL1	NM_014271.4	MANE Select	c.82+65953C>T		intron	N/A	NP_055086.1	X5DNQ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAPL1	ENST00000378993.6	TSL:1 MANE Select	c.82+65953C>T		intron	N/A	ENSP00000368278.1	Q9NZN1-1

Frequencies

GnomAD3 genomes AF: 0.519 AC: 56330 AN: 108528 Hom.: 12370 Cov.: 21

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.519 AC: 56375 AN: 108574 Hom.: 12379 Cov.: 21 AF XY: 0.511 AC XY: 15821 AN XY: 30956

African (AFR) AF: 0.825 AC: 24603 AN: 29833

American (AMR) AF: 0.513 AC: 5184 AN: 10107

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1228 AN: 2609

East Asian (EAS) AF: 0.806 AC: 2753 AN: 3414

South Asian (SAS) AF: 0.410 AC: 1021 AN: 2491

European-Finnish (FIN) AF: 0.350 AC: 1932 AN: 5518

Middle Eastern (MID) AF: 0.417 AC: 88 AN: 211

European-Non Finnish (NFE) AF: 0.357 AC: 18635 AN: 52252

Other (OTH) AF: 0.508 AC: 745 AN: 1467

Alfa AF: 0.439 Hom.: 4049

Bravo AF: 0.556

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.83
DANN	Benign	0.57
PhyloP100		-1.1
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: rs1318832; hg19: chrX-28873495;