chrX-28789354-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_014271.4(IL1RAPL1):c.11C>T(p.Pro4Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000937 in 1,205,768 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 40 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P4P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000098 ( 0 hom. 40 hem. )

Consequence

IL1RAPL1
NM_014271.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.16

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

intellectual disability, X-linked 21
Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
non-syndromic X-linked intellectual disability
Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet

IL1RAPL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13727984).

BP6

Variant X-28789354-C-T is Benign according to our data. Variant chrX-28789354-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 2056458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAdExome4 at 40 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014271.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAPL1	NM_014271.4	MANE Select	c.11C>T	p.Pro4Leu	missense	Exon 2 of 11	NP_055086.1	X5DNQ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAPL1	ENST00000378993.6	TSL:1 MANE Select	c.11C>T	p.Pro4Leu	missense	Exon 2 of 11	ENSP00000368278.1	Q9NZN1-1

Frequencies

GnomAD3 genomes

AF:

0.0000537

AC:

AN:

111740

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000955

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000941

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000764

AC:

AN:

183259

AF XY:

0.000103

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.0000978

AC:

107

AN:

1094028

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

359668

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26302

American (AMR)

AF:

0.0000284

AC:

AN:

35188

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19344

East Asian (EAS)

AF:

0.00

AC:

AN:

30137

South Asian (SAS)

AF:

0.00

AC:

AN:

54035

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40449

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4109

European-Non Finnish (NFE)

AF:

0.000124

AC:

104

AN:

838521

Other (OTH)

AF:

0.0000435

AC:

AN:

45943

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.434

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000537

AC:

AN:

111740

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33930

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30774

American (AMR)

AF:

0.0000955

AC:

AN:

10472

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.00

AC:

AN:

3566

South Asian (SAS)

AF:

0.00

AC:

AN:

2692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6000

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.0000941

AC:

AN:

53161

Other (OTH)

AF:

0.00

AC:

AN:

1507

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.0000340

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.41

DEOGEN2

Benign

0.16

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.74

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.22

PhyloP100

4.2

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.19

REVEL

Benign

0.097

Sift

Benign

0.33

Sift4G

Benign

0.70

Polyphen

0.0020

Vest4

0.36

MVP

0.57

MPC

0.86

ClinPred

0.090

GERP RS

4.9

Varity_R

0.17

gMVP

0.55

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over