X-29710354-GTTT-GTTTTT

Variant names:

• chrX-29710354-G-GTT
• rs11385352
• NM_014271.4:c.778+41860_778+41861dupTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_014271.4(IL1RAPL1):​c.778+41860_778+41861dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00056 (0 hom., 15 hem., cov: 0)
• Consequence: IL1RAPL1 NM_014271.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.208
• Publications: 1 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: Orphanet, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAd4 at 15 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RAPL1	NM_014271.4	c.778+41860_778+41861dupTT		intron_variant	Intron 6 of 10	ENST00000378993.6	NP_055086.1
IL1RAPL1	XM_017029240.2	c.778+41860_778+41861dupTT		intron_variant	Intron 6 of 10		XP_016884729.1
IL1RAPL1	XM_017029241.2	c.400+41860_400+41861dupTT		intron_variant	Intron 4 of 8		XP_016884730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RAPL1	ENST00000378993.6	c.778+41850_778+41851insTT		intron_variant	Intron 6 of 10	1	NM_014271.4	ENSP00000368278.1

Frequencies

GnomAD3 genomes AF: 0.000549 AC: 55 AN: 100170 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000287

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00317

Gnomad ASJ AF: 0.000405

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00134

Gnomad FIN AF: 0.000279

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000222

Gnomad OTH AF: 0.00151

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.000559 AC: 56 AN: 100171 Hom.: 0 Cov.: 0 AF XY: 0.000584 AC XY: 15 AN XY: 25681

African (AFR) AF: 0.000323 AC: 9 AN: 27893

American (AMR) AF: 0.00316 AC: 29 AN: 9169

Ashkenazi Jewish (ASJ) AF: 0.000405 AC: 1 AN: 2470

East Asian (EAS) AF: 0.00 AC: 0 AN: 3194

South Asian (SAS) AF: 0.00135 AC: 3 AN: 2230

European-Finnish (FIN) AF: 0.000279 AC: 1 AN: 3590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 185

European-Non Finnish (NFE) AF: 0.000222 AC: 11 AN: 49450

Other (OTH) AF: 0.00149 AC: 2 AN: 1345

Alfa AF: 0.00 Hom.: 920

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11385352; hg19: chrX-29728471;