X-28853122-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014271.4(IL1RAPL1):c.82+63697C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.021 (75 hom., 499 hem., cov: 20)
• Consequence: IL1RAPL1 NM_014271.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.308

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant X-28853122-C-G is Benign according to our data. Variant chrX-28853122-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1321729.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RAPL1	NM_014271.4	c.82+63697C>G		intron_variant		ENST00000378993.6
IL1RAPL1	XM_017029240.2	c.82+63697C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RAPL1	ENST00000378993.6	c.82+63697C>G		intron_variant		1	NM_014271.4	P1

Frequencies

GnomAD3 genomes AF: 0.0207 AC: 1457 AN: 70295 Hom.: 76 Cov.: 20 AF XY: 0.0300 AC XY: 499 AN XY: 16625

Gnomad AFR AF: 0.00752

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0393

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.0912

Gnomad FIN AF: 0.00114

Gnomad MID AF: 0.0110

Gnomad NFE AF: 0.00102

Gnomad OTH AF: 0.0215

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

GnomAD4 genome AF: 0.0207 AC: 1452 AN: 70283 Hom.: 75 Cov.: 20 AF XY: 0.0300 AC XY: 499 AN XY: 16649

Gnomad4 AFR AF: 0.00751

Gnomad4 AMR AF: 0.0389

Gnomad4 ASJ AF: 0.00374

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.0917

Gnomad4 FIN AF: 0.00114

Gnomad4 NFE AF: 0.00102

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.00407 Hom.: 16

Bravo AF: 0.0172

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.20
Dann	Benign	0.42

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: rs140239490; hg19: chrX-28871239;