rs9298814

chr9-21227623-A-Cchr9-21227623-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021268.2(IFNA17):c.551T>G(p.Ile184Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,473,920 control chromosomes in the GnomAD database, including 47,321 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I184M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.28 (6531 hom., cov: 32)
  • Exomes 𝑓: 0.20 (40790 hom.)
• Consequence: IFNA17 NM_021268.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.760

Genes affected

IFNA17 (HGNC:5422): (interferon alpha 17) Predicted to enable cytokine activity and type I interferon receptor binding activity. Predicted to be involved in several processes, including B cell activation; lymphocyte activation involved in immune response; and positive regulation of peptidyl-serine phosphorylation of STAT protein. Predicted to be located in extracellular region. Predicted to be active in extracellular space. Implicated in Crimean-Congo hemorrhagic fever and sarcoidosis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011078656).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNA17	NM_021268.2	c.551T>G	p.Ile184Arg	missense_variant	1/1	ENST00000413767.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNA17	ENST00000413767.2	c.551T>G	p.Ile184Arg	missense_variant	1/1		NM_021268.2	P1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42376 AN: 151646 Hom.: 6522 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.269

GnomAD3 exomes AF: 0.116 AC: 26310 AN: 226892 Hom.: 5071 AF XY: 0.103 AC XY: 12728 AN XY: 123150

Gnomad AFR exome AF: 0.212

Gnomad AMR exome AF: 0.151

Gnomad ASJ exome AF: 0.0652

Gnomad EAS exome AF: 0.354

Gnomad SAS exome AF: 0.0569

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.0772

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.198 AC: 261478 AN: 1322160 Hom.: 40790 Cov.: 33 AF XY: 0.196 AC XY: 129582 AN XY: 660462

Gnomad4 AFR exome AF: 0.350

Gnomad4 AMR exome AF: 0.312

Gnomad4 ASJ exome AF: 0.213

Gnomad4 EAS exome AF: 0.548

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.197

Gnomad4 NFE exome AF: 0.177

Gnomad4 OTH exome AF: 0.215

GnomAD4 genome AF: 0.280 AC: 42426 AN: 151760 Hom.: 6531 Cov.: 32 AF XY: 0.279 AC XY: 20687 AN XY: 74136

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.268

Alfa AF: 0.111 Hom.: 333

Bravo AF: 0.295

ESP6500AA AF: 0.130 AC: 572

ESP6500EA AF: 0.0527 AC: 453

ExAC AF: 0.0812 AC: 9844

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.042
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
Cadd	Benign	0.82
Dann	Benign	0.54
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.000070	N
LIST_S2	Benign	0.066	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-3.5	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.44	T
PROVEAN	Benign	5.5	N
REVEL	Benign	0.041
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.044
MPC		0.015
ClinPred		0.0079	T
GERP RS		0.95
Varity_R		0.037
gMVP		0.033

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs9298814; hg19: chr9-21227622; COSMIC: COSV69738214; COSMIC: COSV69738214;