chr3-190632672-A-G

Variant names:

• chr3-190632672-A-G
• rs7626795
• NM_002182.4:c.1051+3174A>G

Variant summary

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

The NM_002182.4(IL1RAP):​c.1051+3174A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,152 control chromosomes in the GnomAD database, including 5,305 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 0.23 (5305 hom., cov: 33)
• Consequence: IL1RAP NM_002182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.343
• Publications: 29 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.427 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAP	NM_002182.4	MANE Select	c.1051+3174A>G		intron	N/A	NP_002173.1
	IL1RAP	NM_001167931.2		c.1051+3174A>G		intron	N/A	NP_001161403.1
	IL1RAP	NM_001364879.1		c.1051+3174A>G		intron	N/A	NP_001351808.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAP	ENST00000447382.6	TSL:1 MANE Select	c.1051+3174A>G		intron	N/A	ENSP00000390541.1
	IL1RAP	ENST00000317757.8	TSL:1	c.1051+3174A>G		intron	N/A	ENSP00000314807.3
	IL1RAP	ENST00000072516.7	TSL:1	c.1051+3174A>G		intron	N/A	ENSP00000072516.3

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34408 AN: 152034 Hom.: 5269 Cov.: 33

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.0940

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.227 AC: 34504 AN: 152152 Hom.: 5305 Cov.: 33 AF XY: 0.226 AC XY: 16805 AN XY: 74382

African (AFR) AF: 0.433 AC: 17952 AN: 41482

American (AMR) AF: 0.253 AC: 3868 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 604 AN: 3468

East Asian (EAS) AF: 0.172 AC: 890 AN: 5176

South Asian (SAS) AF: 0.232 AC: 1119 AN: 4818

European-Finnish (FIN) AF: 0.0940 AC: 996 AN: 10596

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8480 AN: 67996

Other (OTH) AF: 0.208 AC: 440 AN: 2116

Alfa AF: 0.165 Hom.: 10254

Bravo AF: 0.248

Asia WGS AF: 0.206 AC: 715 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.4
DANN	Benign	0.75
PhyloP100		0.34
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: rs7626795; hg19: chr3-190350461;