chrX-28840673-C-T

Variant names:

• chrX-28840673-C-T
• rs4893596
• NM_014271.4:c.82+51248C>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+51248C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 110,271 control chromosomes in the GnomAD database, including 1,348 homozygotes. There are 3,775 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 0.12 (1348 hom., 3775 hem., cov: 22)
• Consequence: IL1RAPL1 NM_014271.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• 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 = 0.319 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+51248C>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+51248C>T		intron	N/A	ENSP00000368278.1	Q9NZN1-1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 13208 AN: 110228 Hom.: 1350 Cov.: 22

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.0597

Gnomad AMR AF: 0.0731

Gnomad ASJ AF: 0.0524

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0207

Gnomad MID AF: 0.0468

Gnomad NFE AF: 0.0137

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.120 AC: 13210 AN: 110271 Hom.: 1348 Cov.: 22 AF XY: 0.115 AC XY: 3775 AN XY: 32865

African (AFR) AF: 0.324 AC: 9857 AN: 30378

American (AMR) AF: 0.0728 AC: 751 AN: 10321

Ashkenazi Jewish (ASJ) AF: 0.0524 AC: 137 AN: 2615

East Asian (EAS) AF: 0.312 AC: 1086 AN: 3479

South Asian (SAS) AF: 0.119 AC: 321 AN: 2689

European-Finnish (FIN) AF: 0.0207 AC: 123 AN: 5931

Middle Eastern (MID) AF: 0.0465 AC: 10 AN: 215

European-Non Finnish (NFE) AF: 0.0137 AC: 719 AN: 52459

Other (OTH) AF: 0.110 AC: 165 AN: 1497

Alfa AF: 0.0616 Hom.: 511

Bravo AF: 0.137

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.14
DANN	Benign	0.35
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: rs4893596; hg19: chrX-28858790;