NM_017416.2:c.83-32544C>T

Variant names:

• chrX-105162931-C-T
• rs5916727
• NM_017416.2:c.83-32544C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_017416.2(IL1RAPL2):​c.83-32544C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 111,265 control chromosomes in the GnomAD database, including 11 homozygotes. There are 296 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.011 (11 hom., 296 hem., cov: 22)
• Consequence: IL1RAPL2 NM_017416.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0106 (1179/111265) while in subpopulation NFE AF = 0.0169 (896/53014). AF 95% confidence interval is 0.016. There are 11 homozygotes in GnomAd4. There are 296 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RAPL2	NM_017416.2	c.83-32544C>T		intron_variant	Intron 2 of 10	ENST00000372582.6	NP_059112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RAPL2	ENST00000372582.6	c.83-32544C>T		intron_variant	Intron 2 of 10	1	NM_017416.2	ENSP00000361663.1

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1179 AN: 111209 Hom.: 11 Cov.: 22

Gnomad AFR AF: 0.00278

Gnomad AMI AF: 0.0799

Gnomad AMR AF: 0.00912

Gnomad ASJ AF: 0.00340

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00151

Gnomad FIN AF: 0.00464

Gnomad MID AF: 0.00424

Gnomad NFE AF: 0.0169

Gnomad OTH AF: 0.00474

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

GnomAD4 genome AF: 0.0106 AC: 1179 AN: 111265 Hom.: 11 Cov.: 22 AF XY: 0.00884 AC XY: 296 AN XY: 33497

African (AFR) AF: 0.00278 AC: 85 AN: 30606

American (AMR) AF: 0.00911 AC: 95 AN: 10431

Ashkenazi Jewish (ASJ) AF: 0.00340 AC: 9 AN: 2644

East Asian (EAS) AF: 0.00 AC: 0 AN: 3519

South Asian (SAS) AF: 0.00152 AC: 4 AN: 2634

European-Finnish (FIN) AF: 0.00464 AC: 28 AN: 6030

Middle Eastern (MID) AF: 0.00463 AC: 1 AN: 216

European-Non Finnish (NFE) AF: 0.0169 AC: 896 AN: 53014

Other (OTH) AF: 0.00468 AC: 7 AN: 1495

Alfa AF: 0.0117 Hom.: 85

Bravo AF: 0.0113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.66
DANN	Benign	0.51
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs5916727; hg19: chrX-104407614;