chr9-21440530-T-G

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_024013.3(IFNA1):c.23T>G(p.Leu8Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 28)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

IFNA1
NM_024013.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.740

Publications

0 publications found

Variant links:

Genes affected

IFNA1 (HGNC:5417): (interferon alpha 1) 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. This cytokine is upregulated in preeclamptic placentas and is thought to be a mediator of preeclampsia. [provided by RefSeq, Aug 2020]

IFNA1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.97

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024013.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNA1	NM_024013.3	MANE Select	c.23T>G	p.Leu8Arg	missense	Exon 1 of 1	NP_076918.1	P01562

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IFNA1	ENST00000276927.3	TSL:6 MANE Select	c.23T>G	p.Leu8Arg	missense	Exon 1 of 1	ENSP00000276927.1	P01562
MIR31HG	ENST00000698348.1		n.725A>C		non_coding_transcript_exon	Exon 3 of 3
MIR31HG	ENST00000698343.1		n.103-19838A>C		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251210

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000267

AC:

AN:

1461852

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000342

AC:

AN:

1111984

Other (OTH)

AF:

0.0000166

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.71

M_CAP

Benign

0.011

MetaRNN

Pathogenic

0.97

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.7

PhyloP100

0.74

PrimateAI

Benign

0.28

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.17

Sift

Uncertain

0.0040

Sift4G

Pathogenic

0.0010

Polyphen

0.97

Vest4

0.68

MutPred

0.88

Gain of methylation at L8 (P = 0.0185)

MVP

0.28

MPC

3.1

ClinPred

0.58

GERP RS

0.92

PromoterAI

0.0064

Neutral

(source)

Varity_R

0.23

gMVP

0.68

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over