NM_014271.4:c.703+69730G>A

Variant names:

• chrX-29469038-G-A
• rs715328
• NM_014271.4:c.703+69730G>A

Variant summary

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

The NM_014271.4(IL1RAPL1):​c.703+69730G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 110,435 control chromosomes in the GnomAD database, including 7,451 homozygotes. There are 13,668 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 0.42 (7451 hom., 13668 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: Orphanet, ClinGen

ENSG00000309436 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RAPL1	NM_014271.4	c.703+69730G>A		intron_variant	Intron 5 of 10	ENST00000378993.6	NP_055086.1
IL1RAPL1	XM_017029240.2	c.703+69730G>A		intron_variant	Intron 5 of 10		XP_016884729.1
IL1RAPL1	XM_017029241.2	c.325+69730G>A		intron_variant	Intron 3 of 8		XP_016884730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RAPL1	ENST00000378993.6	c.703+69730G>A		intron_variant	Intron 5 of 10	1	NM_014271.4	ENSP00000368278.1
ENSG00000309436	ENST00000841139.1	n.110+9570C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 46088 AN: 110383 Hom.: 7451 Cov.: 23

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.470

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.417 AC: 46091 AN: 110435 Hom.: 7451 Cov.: 23 AF XY: 0.418 AC XY: 13668 AN XY: 32715

African (AFR) AF: 0.238 AC: 7254 AN: 30436

American (AMR) AF: 0.339 AC: 3518 AN: 10381

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1372 AN: 2632

East Asian (EAS) AF: 0.750 AC: 2604 AN: 3470

South Asian (SAS) AF: 0.651 AC: 1679 AN: 2581

European-Finnish (FIN) AF: 0.551 AC: 3191 AN: 5788

Middle Eastern (MID) AF: 0.433 AC: 93 AN: 215

European-Non Finnish (NFE) AF: 0.484 AC: 25521 AN: 52727

Other (OTH) AF: 0.431 AC: 656 AN: 1523

Alfa AF: 0.263 Hom.: 1320

Bravo AF: 0.393

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.65
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: rs715328; hg19: chrX-29487155;