X-105195709-C-T

Variant summary

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

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.60

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]

ACMG classification

Verdict is Benign. Variant got -10 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_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd at 36 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RAPL2	NM_017416.2	c.317C>T	p.Ala106Val	missense_variant	3/11	ENST00000372582.6

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00145 AC: 163 AN: 112244 Hom.: 0 Cov.: 23 AF XY: 0.00105 AC XY: 36 AN XY: 34404

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.: 0 AF XY: 0.00103 AC XY: 70 AN XY: 67804

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.: 5 Cov.: 30 AF XY: 0.00267 AC XY: 970 AN XY: 363266

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.: 0 Cov.: 23 AF XY: 0.00104 AC XY: 36 AN XY: 34472

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.: 94

Bravo AF: 0.00127

TwinsUK AF: 0.00297 AC: 11

ALSPAC AF: 0.00658 AC: 19

ESP6500AA AF: 0.000782 AC: 3

ESP6500EA AF: 0.00342 AC: 23

ExAC AF: 0.00101 AC: 122

EpiCase AF: 0.00229

EpiControl AF: 0.00130

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	20
Dann	Uncertain	1.0
DEOGEN2	Benign	0.069	T
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.10
Sift	Benign	0.16	T
Sift4G	Benign	0.10	T
Polyphen		0.0060	B
Vest4		0.21
MVP		0.52
MPC		1.1
ClinPred		0.031	T
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

Other links and lift over

dbSNP: rs144175494; hg19: chrX-104440391;