rs2383183

Variant names:

• chr9-21187701-T-C
• rs2383183
• NM_021068.4:c.-170A>G

Variant summary

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

The NM_021068.4(IFNA4):​c.-170A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.099 in 1,089,644 control chromosomes in the GnomAD database, including 5,658 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 0.080 (657 hom., cov: 32)
  • Exomes 𝑓: 0.10 (5001 hom.)
• Consequence: IFNA4 NM_021068.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.825
• Publications: 8 publications found

Genes affected

IFNA4 (HGNC:5425): (interferon alpha 4) 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. [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 (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNA4	NM_021068.4	c.-170A>G		upstream_gene_variant		ENST00000421715.3	NP_066546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNA4	ENST00000421715.3	c.-170A>G		upstream_gene_variant		6	NM_021068.4	ENSP00000412897.1

Frequencies

GnomAD3 genomes AF: 0.0798 AC: 12151 AN: 152190 Hom.: 656 Cov.: 32

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0823

Gnomad ASJ AF: 0.0991

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0502

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0790

GnomAD4 exome AF: 0.102 AC: 95678 AN: 937336 Hom.: 5001 Cov.: 13 AF XY: 0.101 AC XY: 46510 AN XY: 459970

African (AFR) AF: 0.0147 AC: 318 AN: 21584

American (AMR) AF: 0.0714 AC: 1202 AN: 16832

Ashkenazi Jewish (ASJ) AF: 0.0976 AC: 1577 AN: 16164

East Asian (EAS) AF: 0.165 AC: 5424 AN: 32930

South Asian (SAS) AF: 0.0541 AC: 2181 AN: 40334

European-Finnish (FIN) AF: 0.106 AC: 4577 AN: 43158

Middle Eastern (MID) AF: 0.0597 AC: 173 AN: 2900

European-Non Finnish (NFE) AF: 0.106 AC: 76312 AN: 722050

Other (OTH) AF: 0.0946 AC: 3914 AN: 41384

GnomAD4 genome AF: 0.0798 AC: 12159 AN: 152308 Hom.: 657 Cov.: 32 AF XY: 0.0803 AC XY: 5978 AN XY: 74460

African (AFR) AF: 0.0188 AC: 784 AN: 41600

American (AMR) AF: 0.0822 AC: 1257 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0991 AC: 344 AN: 3472

East Asian (EAS) AF: 0.167 AC: 863 AN: 5174

South Asian (SAS) AF: 0.0515 AC: 249 AN: 4834

European-Finnish (FIN) AF: 0.114 AC: 1203 AN: 10598

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7143 AN: 68024

Other (OTH) AF: 0.0801 AC: 169 AN: 2110

Alfa AF: 0.0911 Hom.: 144

Bravo AF: 0.0739

Asia WGS AF: 0.115 AC: 402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.57
DANN	Benign	0.64
PhyloP100		-0.82
PromoterAI		0.0056	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2383183; hg19: chr9-21187700; COSMIC: COSV70179660;