NM_014271.4:c.-19G>A

Variant names:

• chrX-28789325-G-A
• rs6526806
• NM_014271.4:c.-19G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BP6_Very_Strong

The NM_014271.4(IL1RAPL1):​c.-19G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (17099 hom., 20472 hem., cov: 23)
  • Exomes 𝑓: 0.52 (99590 hom. 169950 hem.)
  • Failed GnomAD Quality Control
• Consequence: IL1RAPL1 NM_014271.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.755
• Publications: 13 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• non-syndromic X-linked intellectual disability

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant X-28789325-G-A is Benign according to our data. Variant chrX-28789325-G-A is described in ClinVar as Benign. ClinVar VariationId is 281021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.-19G>A		5_prime_UTR	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.-19G>A		5_prime_UTR	Exon 2 of 11	ENSP00000368278.1	Q9NZN1-1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 69709 AN: 110355 Hom.: 17086 Cov.: 23

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.629

GnomAD2 exomes AF: 0.585 AC: 105986 AN: 181267 AF XY: 0.574

Gnomad AFR exome AF: 0.916

Gnomad AMR exome AF: 0.616

Gnomad ASJ exome AF: 0.636

Gnomad EAS exome AF: 0.838

Gnomad FIN exome AF: 0.461

Gnomad NFE exome AF: 0.492

Gnomad OTH exome AF: 0.571

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.524 AC: 539644 AN: 1028904 Hom.: 99590 Cov.: 20 AF XY: 0.538 AC XY: 169950 AN XY: 315748

African (AFR) AF: 0.922 AC: 23336 AN: 25314

American (AMR) AF: 0.614 AC: 21467 AN: 34990

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 12083 AN: 18957

East Asian (EAS) AF: 0.822 AC: 24552 AN: 29886

South Asian (SAS) AF: 0.620 AC: 32592 AN: 52597

European-Finnish (FIN) AF: 0.450 AC: 18135 AN: 40304

Middle Eastern (MID) AF: 0.697 AC: 2747 AN: 3939

European-Non Finnish (NFE) AF: 0.487 AC: 379546 AN: 779031

Other (OTH) AF: 0.574 AC: 25186 AN: 43886

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.632 AC: 69766 AN: 110401 Hom.: 17099 Cov.: 23 AF XY: 0.627 AC XY: 20472 AN XY: 32645

African (AFR) AF: 0.908 AC: 27683 AN: 30478

American (AMR) AF: 0.599 AC: 6171 AN: 10305

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 1729 AN: 2639

East Asian (EAS) AF: 0.847 AC: 2976 AN: 3515

South Asian (SAS) AF: 0.609 AC: 1580 AN: 2593

European-Finnish (FIN) AF: 0.458 AC: 2639 AN: 5764

Middle Eastern (MID) AF: 0.690 AC: 147 AN: 213

European-Non Finnish (NFE) AF: 0.487 AC: 25659 AN: 52715

Other (OTH) AF: 0.633 AC: 952 AN: 1505

Alfa AF: 0.550 Hom.: 38641

Bravo AF: 0.660

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Intellectual disability, X-linked 21 (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.76
Mutation Taster		=300/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6526806; hg19: chrX-28807442;