9-21385313-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000605.4(IFNA2):c.17C>A(p.Ala6Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,612,332 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0069 ( 19 hom., cov: 32)

Exomes 𝑓: 0.00074 ( 17 hom. )

Consequence

IFNA2
NM_000605.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.614

Variant links:

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]

IFNA2 links:

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]

MIR31HG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034146905).

BP6

Variant 9-21385313-G-T is Benign according to our data. Variant chr9-21385313-G-T is described in ClinVar as [Benign]. Clinvar id is 778412.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00689 (1049/152256) while in subpopulation AFR AF= 0.0243 (1008/41536). AF 95% confidence interval is 0.023. There are 19 homozygotes in gnomad4. There are 478 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNA2	NM_000605.4 link	c.17C>A	p.Ala6Asp	missense_variant	Exon 1 of 1	ENST00000380206.4	NP_000596.2	P01563A0A7R8GUN5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNA2	ENST00000380206.4 link	c.17C>A	p.Ala6Asp	missense_variant	Exon 1 of 1	6	NM_000605.4	ENSP00000369554.2		P01563
MIR31HG	ENST00000698342.1 link	n.726-4954C>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.00689

AC:

1048

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00764

GnomAD3 exomes

AF:

0.00193

AC:

480

AN:

249280

Hom.:

AF XY:

0.00135

AC XY:

182

AN XY:

134714

show subpopulations

Gnomad AFR exome

AF:

0.0265

Gnomad AMR exome

AF:

0.00102

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000658

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000532

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.000742

AC:

1084

AN:

1460076

Hom.:

Cov.:

AF XY:

0.000658

AC XY:

478

AN XY:

726340

show subpopulations

Gnomad4 AFR exome

AF:

0.0259

Gnomad4 AMR exome

AF:

0.00122

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000581

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000657

Gnomad4 OTH exome

AF:

0.00141

GnomAD4 genome

AF:

0.00689

AC:

1049

AN:

152256

Hom.:

Cov.:

AF XY:

0.00642

AC XY:

478

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0243

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.00804

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0227

AC:

100

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00237

AC:

288

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 21, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.90

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.046

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.96

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.9

REVEL

Benign

0.085

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.029

Vest4

0.17

MVP

0.16

MPC

0.0021

ClinPred

0.033

GERP RS

1.3

gMVP

0.41

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over