rs148060509

Positions:

chrX-28789379-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_014271.4(IL1RAPL1):c.36C>T(p.Tyr12=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 1,208,183 control chromosomes in the GnomAD database, including 3 homozygotes. There are 592 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., 39 hem., cov: 23)

Exomes 𝑓: 0.0015 ( 3 hom. 553 hem. )

Consequence

IL1RAPL1
NM_014271.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.40

Variant links:

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]

IL1RAPL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant X-28789379-C-T is Benign according to our data. Variant chrX-28789379-C-T is described in ClinVar as [Benign]. Clinvar id is 368189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-28789379-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.4 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 39 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RAPL1	NM_014271.4 linkuse as main transcript	c.36C>T	p.Tyr12=	synonymous_variant	2/11	ENST00000378993.6	NP_055086.1
IL1RAPL1	XM_017029240.2 linkuse as main transcript	c.36C>T	p.Tyr12=	synonymous_variant	2/11		XP_016884729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RAPL1	ENST00000378993.6 linkuse as main transcript	c.36C>T	p.Tyr12=	synonymous_variant	2/11	1	NM_014271.4	ENSP00000368278	P1	Q9NZN1-1

Frequencies

GnomAD3 genomes

AF:

0.00127

AC:

142

AN:

112000

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

34178

show subpopulations

Gnomad AFR

AF:

0.000292

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00133

Gnomad ASJ

AF:

0.0102

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000165

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00162

Gnomad OTH

AF:

0.00331

GnomAD3 exomes

AF:

0.00173

AC:

318

AN:

183373

Hom.:

AF XY:

0.00159

AC XY:

108

AN XY:

67833

show subpopulations

Gnomad AFR exome

AF:

0.000380

Gnomad AMR exome

AF:

0.00157

Gnomad ASJ exome

AF:

0.0116

Gnomad EAS exome

AF:

0.0000722

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.000438

Gnomad NFE exome

AF:

0.00203

Gnomad OTH exome

AF:

0.00155

GnomAD4 exome

AF:

0.00152

AC:

1671

AN:

1096129

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

553

AN XY:

361615

show subpopulations

Gnomad4 AFR exome

AF:

0.000304

Gnomad4 AMR exome

AF:

0.00153

Gnomad4 ASJ exome

AF:

0.0116

Gnomad4 EAS exome

AF:

0.000199

Gnomad4 SAS exome

AF:

0.000111

Gnomad4 FIN exome

AF:

0.000494

Gnomad4 NFE exome

AF:

0.00149

Gnomad4 OTH exome

AF:

0.00215

GnomAD4 genome

AF:

0.00127

AC:

142

AN:

112054

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

34242

show subpopulations

Gnomad4 AFR

AF:

0.000291

Gnomad4 AMR

AF:

0.00133

Gnomad4 ASJ

AF:

0.0102

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000165

Gnomad4 NFE

AF:

0.00162

Gnomad4 OTH

AF:

0.00327

Alfa

AF:

0.00258

Hom.:

Bravo

AF:

0.00138

EpiCase

AF:

0.00207

EpiControl

AF:

0.00148

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 24, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 30, 2016

- -

Intellectual disability, X-linked 21

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

4.5

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over