X-28587759-GT-G

Position:

• chrX-28587759-GT-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014271.4(IL1RAPL1):​c.-302del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.59 (13956 hom., 14881 hem., cov: 0)
  • Exomes 𝑓: 0.20 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: IL1RAPL1 NM_014271.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0760

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 -10 ACMG points.

• BP6: Variant X-28587759-GT-G is Benign according to our data. Variant chrX-28587759-GT-G is described in ClinVar as [Benign]. Clinvar id is 368183.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-28587759-GT-G is described in Lovd as [Likely_benign].
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RAPL1	NM_014271.4	c.-302del		5_prime_UTR_variant	1/11	ENST00000378993.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RAPL1	ENST00000378993.6	c.-302del		5_prime_UTR_variant	1/11	1	NM_014271.4	P1

Frequencies

GnomAD3 genomes AF: 0.595 AC: 60513 AN: 101770 Hom.: 13956 Cov.: 0 AF XY: 0.573 AC XY: 14870 AN XY: 25938

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.480

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.582

GnomAD4 exome AF: 0.200 AC: 1 AN: 5 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 3

Gnomad4 NFE exome AF: 0.200

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.595 AC: 60515 AN: 101775 Hom.: 13956 Cov.: 0 AF XY: 0.573 AC XY: 14881 AN XY: 25955

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.577

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Non-syndromic X-linked intellectual disability Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs779869307; hg19: chrX-28605876;