dbSNP rs148390300: IL1RAPL2:p.Leu6Phe (chrX-104658929-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_017416.2(IL1RAPL2):c.16C>T(p.Leu6Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000378 in 1,203,410 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 147 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., 9 hem., cov: 24)

Exomes 𝑓: 0.00038 ( 0 hom. 138 hem. )

Consequence

IL1RAPL2
NM_017416.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.88

Publications

0 publications found

Variant links:

Genes affected

IL1RAPL2 (HGNC:5997): (interleukin 1 receptor accessory protein like 2) The protein encoded by this gene is a member of the interleukin 1 receptor family. This protein is similar to the interleukin 1 accessory proteins, and is most closely related to interleukin 1 receptor accessory protein-like 1 (IL1RAPL1). This gene and IL1RAPL1 are located at a region on chromosome X that is associated with X-linked non-syndromic cognitive disability. [provided by RefSeq, Jul 2008]

IL1RAPL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0075190067).

BP6

Variant X-104658929-C-T is Benign according to our data. Variant chrX-104658929-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 2208312.

BS2

High Hemizygotes in GnomAd4 at 9 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017416.2. 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
	IL1RAPL2	NM_017416.2	MANE Select	c.16C>T	p.Leu6Phe	missense	Exon 2 of 11	NP_059112.1	Q9NP60

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAPL2	ENST00000372582.6	TSL:1 MANE Select	c.16C>T	p.Leu6Phe	missense	Exon 2 of 11	ENSP00000361663.1	Q9NP60

Frequencies

GnomAD3 genomes

AF:

0.000403

AC:

AN:

111766

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000163

Gnomad AMI

AF:

0.0235

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00420

Gnomad NFE

AF:

0.000414

Gnomad OTH

AF:

0.000665

GnomAD2 exomes

AF:

0.000337

AC:

AN:

178003

AF XY:

0.000397

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:

0.0000627

Gnomad NFE exome

AF:

0.000696

Gnomad OTH exome

AF:

0.000454

GnomAD4 exome

AF:

0.000376

AC:

410

AN:

1091644

Hom.:

Cov.:

AF XY:

0.000386

AC XY:

138

AN XY:

357704

show subpopulations

African (AFR)

AF:

0.0000382

AC:

AN:

26167

American (AMR)

AF:

0.00

AC:

AN:

34584

Ashkenazi Jewish (ASJ)

AF:

0.000104

AC:

AN:

19293

East Asian (EAS)

AF:

0.00

AC:

AN:

30095

South Asian (SAS)

AF:

0.0000753

AC:

AN:

53104

European-Finnish (FIN)

AF:

0.000247

AC:

AN:

40503

Middle Eastern (MID)

AF:

0.000243

AC:

AN:

4113

European-Non Finnish (NFE)

AF:

0.000437

AC:

366

AN:

837904

Other (OTH)

AF:

0.000567

AC:

AN:

45881

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

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:

0.000403

AC:

AN:

111766

Hom.:

Cov.:

AF XY:

0.000265

AC XY:

AN XY:

33978

show subpopulations

African (AFR)

AF:

0.000163

AC:

AN:

30743

American (AMR)

AF:

0.00

AC:

AN:

10524

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2634

East Asian (EAS)

AF:

0.00

AC:

AN:

3547

South Asian (SAS)

AF:

0.00

AC:

AN:

2669

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6080

Middle Eastern (MID)

AF:

0.00420

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.000414

AC:

AN:

53146

Other (OTH)

AF:

0.000665

AC:

AN:

1503

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000492

Hom.:

Bravo

AF:

0.000438

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000595

AC:

ExAC

AF:

0.000437

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.40

DEOGEN2

Benign

0.033

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.40

M_CAP

Benign

0.0084

MetaRNN

Benign

0.0075

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.34

PhyloP100

1.9

PrimateAI

Benign

0.46

PROVEAN

Benign

0.47

REVEL

Benign

0.080

Sift

Benign

0.63

Sift4G

Benign

0.71

Polyphen

0.0010

Vest4

0.080

MVP

0.39

MPC

1.1

ClinPred

0.027

GERP RS

2.5

Varity_R

0.073

gMVP

0.69

Mutation Taster

=99/1

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