X-28631675-C-T

Variant names:

• chrX-28631675-C-T
• rs197000
• NM_014271.4:c.-25+43628C>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.-25+43628C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 111,129 control chromosomes in the GnomAD database, including 6,419 homozygotes. There are 13,312 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 0.40 (6419 hom., 13312 hem., cov: 23)
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.518 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.-25+43628C>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.-25+43628C>T		intron	N/A	ENSP00000368278.1	Q9NZN1-1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 43995 AN: 111074 Hom.: 6417 Cov.: 23

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.489

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.396 AC: 44016 AN: 111129 Hom.: 6419 Cov.: 23 AF XY: 0.398 AC XY: 13312 AN XY: 33421

African (AFR) AF: 0.255 AC: 7805 AN: 30649

American (AMR) AF: 0.399 AC: 4200 AN: 10528

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1241 AN: 2632

East Asian (EAS) AF: 0.367 AC: 1281 AN: 3494

South Asian (SAS) AF: 0.541 AC: 1457 AN: 2691

European-Finnish (FIN) AF: 0.488 AC: 2898 AN: 5943

Middle Eastern (MID) AF: 0.481 AC: 102 AN: 212

European-Non Finnish (NFE) AF: 0.456 AC: 24064 AN: 52795

Other (OTH) AF: 0.422 AC: 637 AN: 1509

Alfa AF: 0.434 Hom.: 8898

Bravo AF: 0.381

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.31
DANN	Benign	0.78
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: rs197000; hg19: chrX-28649792;