9-21227087-T-C

Variant names:

• chr9-21227087-T-C
• rs7868588
• NM_021268.2:c.*517A>G

Variant summary

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

The NM_021268.2(IFNA17):​c.*517A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,062 control chromosomes in the GnomAD database, including 4,961 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 0.24 (4961 hom., cov: 32)
• Consequence: IFNA17 NM_021268.2 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.43

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 (BayesDel_noAF=-1.04).
• 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.*517A>G		downstream_gene_variant		ENST00000413767.2	NP_067091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNA17	ENST00000413767.2	c.*517A>G		downstream_gene_variant		6	NM_021268.2	ENSP00000411940.2

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36012 AN: 151944 Hom.: 4955 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.237 AC: 36048 AN: 152062 Hom.: 4961 Cov.: 32 AF XY: 0.238 AC XY: 17722 AN XY: 74324

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.220

Alfa AF: 0.212 Hom.: 456

Bravo AF: 0.249

Asia WGS AF: 0.326 AC: 1132 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.063
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7868588; hg19: chr9-21227086;