Variant X-105195709-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_017416.2(IL1RAPL2):c.317C>T(p.Ala106Val) variant causes a missense change. The variant allele was found at a frequency of 0.00262 in 1,210,206 control chromosomes in the GnomAD database, including 5 homozygotes. There are 1,006 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., 36 hem., cov: 23)

Exomes 𝑓: 0.0027 ( 5 hom. 970 hem. )

Consequence

IL1RAPL2
NM_017416.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.60

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010100216).

BP6

Variant X-105195709-C-T is Benign according to our data. Variant chrX-105195709-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 726619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 36 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RAPL2	NM_017416.2 linkuse as main transcript	c.317C>T	p.Ala106Val	missense_variant	3/11	ENST00000372582.6	NP_059112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RAPL2	ENST00000372582.6 linkuse as main transcript	c.317C>T	p.Ala106Val	missense_variant	3/11	1	NM_017416.2	ENSP00000361663	P1

Frequencies

GnomAD3 genomes

AF:

0.00145

AC:

163

AN:

112244

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

34404

show subpopulations

Gnomad AFR

AF:

0.000518

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000377

Gnomad ASJ

AF:

0.00188

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00248

Gnomad OTH

AF:

0.00398

GnomAD3 exomes

AF:

0.00117

AC:

215

AN:

183334

Hom.:

AF XY:

0.00103

AC XY:

AN XY:

67804

show subpopulations

Gnomad AFR exome

AF:

0.000380

Gnomad AMR exome

AF:

0.000109

Gnomad ASJ exome

AF:

0.00214

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000125

Gnomad NFE exome

AF:

0.00225

Gnomad OTH exome

AF:

0.00110

GnomAD4 exome

AF:

0.00274

AC:

3012

AN:

1097904

Hom.:

Cov.:

AF XY:

0.00267

AC XY:

970

AN XY:

363266

show subpopulations

Gnomad4 AFR exome

AF:

0.000303

Gnomad4 AMR exome

AF:

0.000256

Gnomad4 ASJ exome

AF:

0.00196

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000740

Gnomad4 NFE exome

AF:

0.00340

Gnomad4 OTH exome

AF:

0.00200

GnomAD4 genome

AF:

0.00145

AC:

163

AN:

112302

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

AN XY:

34472

show subpopulations

Gnomad4 AFR

AF:

0.000517

Gnomad4 AMR

AF:

0.000376

Gnomad4 ASJ

AF:

0.00188

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00248

Gnomad4 OTH

AF:

0.00393

Alfa

AF:

0.00241

Hom.:

Bravo

AF:

0.00127

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00658

AC:

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00342

AC:

ExAC

AF:

0.00101

AC:

122

EpiCase

AF:

0.00229

EpiControl

AF:

0.00130

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.069

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.84

MetaRNN

Benign

0.010

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-2.3

REVEL

Benign

0.10

Sift

Benign

0.16

Sift4G

Benign

0.10

Polyphen

0.0060

Vest4

0.21

MVP

0.52

MPC

1.1

ClinPred

0.031

GERP RS

3.4

Varity_R

0.14

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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