X-28587759-GTT-G

Position:

• chrX-28587759-GTT-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_014271.4(IL1RAPL1):​c.-303_-302del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (0 hom., 69 hem., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: IL1RAPL1 NM_014271.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U: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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Hemizygotes in GnomAd4 at 69 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RAPL1	NM_014271.4	c.-303_-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.-303_-302del		5_prime_UTR_variant	1/11	1	NM_014271.4	P1

Frequencies

GnomAD3 genomes AF: 0.00260 AC: 265 AN: 101925 Hom.: 0 Cov.: 0 AF XY: 0.00242 AC XY: 63 AN XY: 26023

Gnomad AFR AF: 0.00871

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00107

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00124

Gnomad SAS AF: 0.000444

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000597

Gnomad OTH AF: 0.00294

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 7 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 5

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.00266 AC: 271 AN: 101929 Hom.: 0 Cov.: 0 AF XY: 0.00265 AC XY: 69 AN XY: 26039

Gnomad4 AFR AF: 0.00891

Gnomad4 AMR AF: 0.00107

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00124

Gnomad4 SAS AF: 0.000447

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000597

Gnomad4 OTH AF: 0.00290

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Non-syndromic X-linked intellectual disability Uncertain:1

Uncertain significance, 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;