3-190656441-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000317757.8(IL1RAP):c.1898A>G(p.Asn633Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00356 in 1,537,200 control chromosomes in the GnomAD database, including 187 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (100 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (87 hom.)
• Consequence: IL1RAP ENST00000317757.8 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.211

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015479624).
• BP6: Variant 3-190656441-A-G is Benign according to our data. Variant chr3-190656441-A-G is described in ClinVar as [Benign]. Clinvar id is 790550.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.064 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RAP	NM_001167931.2	c.1898A>G	p.Asn633Ser	missense_variant	12/12
IL1RAP	NM_001364879.1	c.1898A>G	p.Asn633Ser	missense_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RAP	ENST00000317757.8	c.1898A>G	p.Asn633Ser	missense_variant	12/12	1

Frequencies

GnomAD3 genomes AF: 0.0186 AC: 2829 AN: 152128 Hom.: 95 Cov.: 32

Gnomad AFR AF: 0.0653

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.00391 AC: 555 AN: 141856 Hom.: 14 AF XY: 0.00312 AC XY: 237 AN XY: 75962

Gnomad AFR exome AF: 0.0635

Gnomad AMR exome AF: 0.00236

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000880

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000705

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00188 AC: 2602 AN: 1384954 Hom.: 87 Cov.: 32 AF XY: 0.00163 AC XY: 1115 AN XY: 683398

Gnomad4 AFR exome AF: 0.0685

Gnomad4 AMR exome AF: 0.00266

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000177

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000454

Gnomad4 OTH exome AF: 0.00456

GnomAD4 genome AF: 0.0188 AC: 2868 AN: 152246 Hom.: 100 Cov.: 32 AF XY: 0.0187 AC XY: 1389 AN XY: 74456

Gnomad4 AFR AF: 0.0660

Gnomad4 AMR AF: 0.00523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.00187 Hom.: 9

Bravo AF: 0.0210

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0585 AC: 81

ESP6500EA AF: 0.000629 AC: 2

ExAC AF: 0.00607 AC: 140

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.84
Cadd	Benign	18
Dann	Benign	0.93
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.12	N
MetaRNN	Benign	0.0015	T;T
MetaSVM	Benign	-0.88	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.18	N;N
REVEL	Benign	0.054
Sift	Benign	0.48	T;T
Sift4G	Benign	0.22	T;T
Polyphen		0.0010	B;B
Vest4		0.076
MVP		0.10
MPC		0.22
ClinPred		0.0011	T
GERP RS		1.9
gMVP		0.078

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs74418158; hg19: chr3-190374230;