rs3750479

chr9-21186932-A-Gchr9-21186932-A-T

Variant summary

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

The NM_021068.4(IFNA4):c.*30T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 1,612,506 control chromosomes in the GnomAD database, including 29,893 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 0.22 (4223 hom., cov: 32)
  • Exomes 𝑓: 0.18 (25670 hom.)
• Consequence: IFNA4 NM_021068.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNA4	NM_021068.4	c.*30T>C		3_prime_UTR_variant	1/1	ENST00000421715.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNA4	ENST00000421715.3	c.*30T>C		3_prime_UTR_variant	1/1		NM_021068.4	P1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33823 AN: 151958 Hom.: 4212 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.215

GnomAD3 exomes AF: 0.209 AC: 52319 AN: 250788 Hom.: 6612 AF XY: 0.195 AC XY: 26444 AN XY: 135574

Gnomad AFR exome AF: 0.302

Gnomad AMR exome AF: 0.300

Gnomad ASJ exome AF: 0.188

Gnomad EAS exome AF: 0.435

Gnomad SAS exome AF: 0.113

Gnomad FIN exome AF: 0.192

Gnomad NFE exome AF: 0.163

Gnomad OTH exome AF: 0.185

GnomAD4 exome AF: 0.178 AC: 260189 AN: 1460430 Hom.: 25670 Cov.: 32 AF XY: 0.175 AC XY: 127198 AN XY: 726566

Gnomad4 AFR exome AF: 0.294

Gnomad4 AMR exome AF: 0.293

Gnomad4 ASJ exome AF: 0.192

Gnomad4 EAS exome AF: 0.422

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.165

Gnomad4 OTH exome AF: 0.188

GnomAD4 genome AF: 0.223 AC: 33886 AN: 152076 Hom.: 4223 Cov.: 32 AF XY: 0.223 AC XY: 16604 AN XY: 74324

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.215

Alfa AF: 0.200 Hom.: 623

Bravo AF: 0.233

Asia WGS AF: 0.258 AC: 897 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.46
Dann	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs3750479; hg19: chr9-21186931;