chr9-21385160-T-G

Variant names:

• chr9-21385160-T-G
• NM_000605.4:c.170A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000605.4(IFNA2):​c.170A>C​(p.His57Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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. H57R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: IFNA2 NM_000605.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50

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:37187): (MIR31 host gene) This gene produces a long non-coding RNA that acts as a host gene for miR-31. This transcript may be involved in cellular pluripotency and regulate the differentiation of myoblasts and other tissues. This RNA was found to interact with Polycomb repressive proteins to repression transcription of genes involves in cell senescence. [provided by RefSeq, Dec 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14887482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNA2	NM_000605.4	c.170A>C	p.His57Pro	missense_variant	Exon 1 of 1	ENST00000380206.4	NP_000596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNA2	ENST00000380206.4	c.170A>C	p.His57Pro	missense_variant	Exon 1 of 1	6	NM_000605.4	ENSP00000369554.2
MIR31HG	ENST00000698342.1	n.726-4801A>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461866 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727238

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 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	9.9
DANN	Benign	0.77
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.0087	N
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.92	T
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.046
Sift	Uncertain	0.025	D
Sift4G	Benign	0.093	T
Vest4		0.24
MutPred		0.47		Loss of stability (P = 0.0287);
MVP		0.14
MPC		0.0042
ClinPred		0.69	D
GERP RS		0.69
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-21385159;