X-28789652-T-C

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+227T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 111,224 control chromosomes in the GnomAD database, including 7,837 homozygotes. There are 14,499 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 (7837 hom., 14499 hem., cov: 24)
• Consequence: IL1RAPL1 NM_014271.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.13

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=-0.79).
• BP6: Variant X-28789652-T-C is Benign according to our data. Variant chrX-28789652-T-C is described in ClinVar as [Benign]. Clinvar id is 1283349.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-28789652-T-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RAPL1	NM_014271.4	c.82+227T>C		intron_variant		ENST00000378993.6
IL1RAPL1	XM_017029240.2	c.82+227T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RAPL1	ENST00000378993.6	c.82+227T>C		intron_variant		1	NM_014271.4	P1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 48896 AN: 111179 Hom.: 7825 Cov.: 24 AF XY: 0.434 AC XY: 14483 AN XY: 33383

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.440 AC: 48925 AN: 111224 Hom.: 7837 Cov.: 24 AF XY: 0.434 AC XY: 14499 AN XY: 33438

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.480

Alfa AF: 0.452 Hom.: 4643

Bravo AF: 0.445

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.79
Cadd	Benign	9.2
Dann	Benign	0.73

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: rs12690144; hg19: chrX-28807769;