rs7052954

Variant names:

• chrX-29673400-G-A
• rs7052954
• NM_014271.4:c.778+4896G>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.778+4896G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0861 in 110,914 control chromosomes in the GnomAD database, including 341 homozygotes. There are 2,621 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 0.086 (341 hom., 2621 hem., cov: 23)
• Consequence: IL1RAPL1 NM_014271.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RAPL1	NM_014271.4	c.778+4896G>A		intron_variant	Intron 6 of 10	ENST00000378993.6	NP_055086.1
IL1RAPL1	XM_017029240.2	c.778+4896G>A		intron_variant	Intron 6 of 10		XP_016884729.1
IL1RAPL1	XM_017029241.2	c.400+4896G>A		intron_variant	Intron 4 of 8		XP_016884730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RAPL1	ENST00000378993.6	c.778+4896G>A		intron_variant	Intron 6 of 10	1	NM_014271.4	ENSP00000368278.1

Frequencies

GnomAD3 genomes AF: 0.0861 AC: 9541 AN: 110861 Hom.: 343 Cov.: 23

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0756

Gnomad AMR AF: 0.0730

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0574

Gnomad FIN AF: 0.0271

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.0867

Gnomad OTH AF: 0.0845

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

GnomAD4 genome AF: 0.0861 AC: 9552 AN: 110914 Hom.: 341 Cov.: 23 AF XY: 0.0790 AC XY: 2621 AN XY: 33192

African (AFR) AF: 0.107 AC: 3253 AN: 30512

American (AMR) AF: 0.0729 AC: 760 AN: 10419

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 422 AN: 2630

East Asian (EAS) AF: 0.00 AC: 0 AN: 3557

South Asian (SAS) AF: 0.0587 AC: 153 AN: 2606

European-Finnish (FIN) AF: 0.0271 AC: 159 AN: 5873

Middle Eastern (MID) AF: 0.207 AC: 43 AN: 208

European-Non Finnish (NFE) AF: 0.0867 AC: 4586 AN: 52911

Other (OTH) AF: 0.0821 AC: 124 AN: 1510

Alfa AF: 0.0880 Hom.: 736

Bravo AF: 0.0892

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.74
DANN	Benign	0.65
PhyloP100		-0.22
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: rs7052954; hg19: chrX-29691517;