rs9298814

Variant names:

• chr9-21227623-A-C
• rs9298814
• NM_021268.2:c.551T>G

Your query was ambiguous. Multiple possible variants found:

• chr9-21227623-A-C
• chr9-21227623-A-G

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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 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
• Publications: 23 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IFNA17	NM_021268.2	c.551T>G	p.Ile184Arg	missense_variant	Exon 1 of 1	ENST00000413767.2	NP_067091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNA17	ENST00000413767.2	c.551T>G	p.Ile184Arg	missense_variant	Exon 1 of 1	6	NM_021268.2	ENSP00000411940.2

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

GnomAD2 exomes AF: 0.116 AC: 26310 AN: 226892 AF XY: 0.103

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.350 AC: 10132 AN: 28918

American (AMR) AF: 0.312 AC: 11903 AN: 38098

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 5203 AN: 24482

East Asian (EAS) AF: 0.548 AC: 20687 AN: 37738

South Asian (SAS) AF: 0.167 AC: 13706 AN: 82198

European-Finnish (FIN) AF: 0.197 AC: 10337 AN: 52404

Middle Eastern (MID) AF: 0.184 AC: 930 AN: 5066

European-Non Finnish (NFE) AF: 0.177 AC: 176661 AN: 997710

Other (OTH) AF: 0.215 AC: 11919 AN: 55546

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.377 AC: 15585 AN: 41380

American (AMR) AF: 0.311 AC: 4737 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 836 AN: 3470

East Asian (EAS) AF: 0.518 AC: 2657 AN: 5128

South Asian (SAS) AF: 0.195 AC: 938 AN: 4810

European-Finnish (FIN) AF: 0.209 AC: 2200 AN: 10524

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14686 AN: 67890

Other (OTH) AF: 0.268 AC: 564 AN: 2102

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
PhyloP100		-0.76
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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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