rs148060509

Variant names:

• chrX-28789379-C-T
• rs148060509
• NM_014271.4:c.36C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_014271.4(IL1RAPL1):​c.36C>T​(p.Tyr12Tyr) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.40
• Publications: 0 publications found

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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 368189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.4 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 39 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.36C>T	p.Tyr12Tyr	synonymous	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.36C>T	p.Tyr12Tyr	synonymous	Exon 2 of 11	ENSP00000368278.1	Q9NZN1-1

Frequencies

GnomAD3 genomes AF: 0.00127 AC: 142 AN: 112000 Hom.: 0 Cov.: 23

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

GnomAD2 exomes AF: 0.00173 AC: 318 AN: 183373 AF XY: 0.00159

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 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.: 3 Cov.: 29 AF XY: 0.00153 AC XY: 553 AN XY: 361615

African (AFR) AF: 0.000304 AC: 8 AN: 26351

American (AMR) AF: 0.00153 AC: 54 AN: 35200

Ashkenazi Jewish (ASJ) AF: 0.0116 AC: 225 AN: 19358

East Asian (EAS) AF: 0.000199 AC: 6 AN: 30155

South Asian (SAS) AF: 0.000111 AC: 6 AN: 54097

European-Finnish (FIN) AF: 0.000494 AC: 20 AN: 40486

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4127

European-Non Finnish (NFE) AF: 0.00149 AC: 1252 AN: 840342

Other (OTH) AF: 0.00215 AC: 99 AN: 46013

GnomAD4 genome AF: 0.00127 AC: 142 AN: 112054 Hom.: 0 Cov.: 23 AF XY: 0.00114 AC XY: 39 AN XY: 34242

African (AFR) AF: 0.000291 AC: 9 AN: 30934

American (AMR) AF: 0.00133 AC: 14 AN: 10515

Ashkenazi Jewish (ASJ) AF: 0.0102 AC: 27 AN: 2642

East Asian (EAS) AF: 0.00 AC: 0 AN: 3572

South Asian (SAS) AF: 0.00 AC: 0 AN: 2692

European-Finnish (FIN) AF: 0.000165 AC: 1 AN: 6065

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.00162 AC: 86 AN: 53205

Other (OTH) AF: 0.00327 AC: 5 AN: 1528

Alfa AF: 0.00258 Hom.: 21

Bravo AF: 0.00138

EpiCase AF: 0.00207

EpiControl AF: 0.00148

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Intellectual disability, X-linked 21 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	4.5
DANN	Benign	0.51
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs148060509; hg19: chrX-28807496; COSMIC: COSV100152028;