X-28789631-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_014271.4(IL1RAPL1):c.82+206A>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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.63 (17139 hom., 20792 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: IL1RAPL1 NM_014271.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.259

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant X-28789631-A-G is Benign according to our data. Variant chrX-28789631-A-G is described in ClinVar as [Benign]. Clinvar id is 1237882.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-28789631-A-G is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAd at 17126 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RAPL1	NM_014271.4	c.82+206A>G		intron_variant		ENST00000378993.6
IL1RAPL1	XM_017029240.2	c.82+206A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RAPL1	ENST00000378993.6	c.82+206A>G		intron_variant		1	NM_014271.4	P1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 70097 AN: 111003 Hom.: 17126 Cov.: 23 AF XY: 0.625 AC XY: 20752 AN XY: 33215

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.630

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.632 AC: 70152 AN: 111048 Hom.: 17139 Cov.: 23 AF XY: 0.625 AC XY: 20792 AN XY: 33270

Gnomad4 AFR AF: 0.908

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.846

Gnomad4 SAS AF: 0.630

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.634

Alfa AF: 0.571 Hom.: 6287

Bravo AF: 0.660

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	-0.91
Cadd	Benign	0.57
Dann	Benign	0.35

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: rs6526807; hg19: chrX-28807748;