chr3-190520509-G-A

Variant names:

• chr3-190520509-G-A
• rs17196143
• NM_002182.4:c.-89+6290G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002182.4(IL1RAP):​c.-89+6290G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,160 control chromosomes in the GnomAD database, including 2,265 homozygotes. 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 0.16 (2265 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: IL1RAP NM_002182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136
• Publications: 5 publications found

Genes affected

IL1RAP (HGNC:5995): (interleukin 1 receptor accessory protein) This gene encodes a component of the interleukin 1 receptor complex, which initiates signalling events that result in the activation of interleukin 1-responsive genes. Alternative splicing of this gene results in membrane-bound and soluble isoforms differing in their C-terminus. The ratio of soluble to membrane-bound forms increases during acute-phase induction or stress. [provided by RefSeq, Jul 2018]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002182.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAP	NM_002182.4	MANE Select	c.-89+6290G>A		intron	N/A	NP_002173.1
	IL1RAP	NM_001167931.2		c.-89+6290G>A		intron	N/A	NP_001161403.1
	IL1RAP	NM_001364879.1		c.-2+6290G>A		intron	N/A	NP_001351808.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAP	ENST00000447382.6	TSL:1 MANE Select	c.-89+6290G>A		intron	N/A	ENSP00000390541.1
	IL1RAP	ENST00000317757.8	TSL:1	c.-89+6290G>A		intron	N/A	ENSP00000314807.3
	IL1RAP	ENST00000072516.7	TSL:1	c.-2+6290G>A		intron	N/A	ENSP00000072516.3

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24497 AN: 152042 Hom.: 2265 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0913

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.188

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.161 AC: 24499 AN: 152160 Hom.: 2265 Cov.: 32 AF XY: 0.156 AC XY: 11595 AN XY: 74386

African (AFR) AF: 0.116 AC: 4800 AN: 41516

American (AMR) AF: 0.142 AC: 2167 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 813 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5182

South Asian (SAS) AF: 0.0922 AC: 445 AN: 4828

European-Finnish (FIN) AF: 0.159 AC: 1681 AN: 10592

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13882 AN: 67982

Other (OTH) AF: 0.186 AC: 393 AN: 2114

Alfa AF: 0.180 Hom.: 1928

Bravo AF: 0.158

Asia WGS AF: 0.0490 AC: 175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.1
DANN	Benign	0.74
PhyloP100		-0.14
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: rs17196143; hg19: chr3-190238298;