9-21384364-A-G

Position:

• chr9-21384364-A-G

Variant summary

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

The NM_000605.4(IFNA2):​c.*399T>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 0.147 in 152,502 control chromosomes in the GnomAD database, including 2,067 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 0.15 (2067 hom., cov: 32)
  • Exomes 𝑓: 0.12 (0 hom.)
• Consequence: IFNA2 NM_000605.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

Genes affected

IFNA2 (HGNC:5423): (interferon alpha 2) This gene is a member of the alpha interferon gene cluster on chromosome 9. The encoded cytokine is a member of the type I interferon family that is produced in response to viral infection as a key part of the innate immune response with potent antiviral, antiproliferative and immunomodulatory properties. This cytokine, like other type I interferons, binds a plasma membrane receptor made of IFNAR1 and IFNAR2 that is ubiquitously expressed, and thus is able to act on virtually all body cells. The encoded protein is effective in reducing the symptoms and duration of the common cold and in treating many types of cancer, including some hematological malignancies and solid tumors. A deficiency of type I interferon in the blood is thought to be a hallmark of severe COVID-19 and may provide a rationale for a combined therapeutic approach. [provided by RefSeq, Aug 2020]

MIR31HG (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNA2	NM_000605.4	c.*399T>C		3_prime_UTR_variant	1/1	ENST00000380206.4	NP_000596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNA2	ENST00000380206.4	c.*399T>C		3_prime_UTR_variant	1/1	6	NM_000605.4	ENSP00000369554.2
MIR31HG	ENST00000698342.1	n.726-4005T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22363 AN: 152118 Hom.: 2067 Cov.: 32

Gnomad AFR AF: 0.0486

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.00211

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.121 AC: 32 AN: 264 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 25 AN XY: 200

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.147 AC: 22359 AN: 152238 Hom.: 2067 Cov.: 32 AF XY: 0.146 AC XY: 10840 AN XY: 74444

Gnomad4 AFR AF: 0.0484

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.163

Alfa AF: 0.204 Hom.: 2983

Bravo AF: 0.138

Asia WGS AF: 0.0970 AC: 336 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.65
DANN	Benign	0.72

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: rs10120977; hg19: chr9-21384363; COSMIC: COSV66505930;