rs715328

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-29469038-G-A
• chrX-29469038-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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

Frequencies

GnomAD3 genomes AF: 0.418 AC: 46088 AN: 110383 Hom.: 7451 Cov.: 23 AF XY: 0.418 AC XY: 13659 AN XY: 32653

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

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.750

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.431

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs715328; hg19: chrX-29487155;