X-28789228-G-A

Position:

• chrX-28789228-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014271.4(IL1RAPL1):​c.-24-92G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 513,400 control chromosomes in the GnomAD database, including 38,821 homozygotes. There are 79,014 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (7707 hom., 14188 hem., cov: 23)
  • Exomes 𝑓: 0.48 (31114 hom. 64826 hem.)
• Consequence: IL1RAPL1 NM_014271.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.585

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant X-28789228-G-A is Benign according to our data. Variant chrX-28789228-G-A is described in ClinVar as [Benign]. Clinvar id is 1236336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RAPL1	NM_014271.4	c.-24-92G>A		intron_variant		ENST00000378993.6
IL1RAPL1	XM_017029240.2	c.-24-92G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RAPL1	ENST00000378993.6	c.-24-92G>A		intron_variant		1	NM_014271.4	P1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 48223 AN: 110594 Hom.: 7695 Cov.: 23 AF XY: 0.431 AC XY: 14168 AN XY: 32862

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.632

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.464

GnomAD4 exome AF: 0.481 AC: 193805 AN: 402755 Hom.: 31114 AF XY: 0.487 AC XY: 64826 AN XY: 133069

Gnomad4 AFR exome AF: 0.336

Gnomad4 AMR exome AF: 0.519

Gnomad4 ASJ exome AF: 0.589

Gnomad4 EAS exome AF: 0.456

Gnomad4 SAS exome AF: 0.528

Gnomad4 FIN exome AF: 0.415

Gnomad4 NFE exome AF: 0.481

Gnomad4 OTH exome AF: 0.490

GnomAD4 genome AF: 0.436 AC: 48254 AN: 110645 Hom.: 7707 Cov.: 23 AF XY: 0.431 AC XY: 14188 AN XY: 32923

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.471

Alfa AF: 0.448 Hom.: 4379

Bravo AF: 0.440

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 03, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.44
DANN	Benign	0.58

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: rs12009069; hg19: chrX-28807345;