chr9-21440917-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024013.3(IFNA1):c.410C>T(p.Ala137Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 144,310 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 41 hom., cov: 25)

Exomes 𝑓: 0.0037 ( 57 hom. )

Failed GnomAD Quality Control

Consequence

IFNA1
NM_024013.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.436

Publications

7 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036209226).

BP6

Variant 9-21440917-C-T is Benign according to our data. Variant chr9-21440917-C-T is described in ClinVar as Benign. ClinVar VariationId is 790065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0574 is higher than 0.05.

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.410C>T	p.Ala137Val	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.410C>T	p.Ala137Val	missense	Exon 1 of 1	ENSP00000276927.1	P01562
MIR31HG	ENST00000698348.1		n.338G>A		non_coding_transcript_exon	Exon 3 of 3
MIR31HG	ENST00000698343.1		n.103-20225G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0187

AC:

2702

AN:

144194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0595

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0124

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.00119

Gnomad SAS

AF:

0.00213

Gnomad FIN

AF:

0.000104

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00249

Gnomad OTH

AF:

0.0203

GnomAD2 exomes

AF:

0.00648

AC:

1556

AN:

240248

AF XY:

0.00528

show subpopulations

Gnomad AFR exome

AF:

0.0672

Gnomad AMR exome

AF:

0.00436

Gnomad ASJ exome

AF:

0.0102

Gnomad EAS exome

AF:

0.000829

Gnomad FIN exome

AF:

0.000143

Gnomad NFE exome

AF:

0.00237

Gnomad OTH exome

AF:

0.00636

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00369

AC:

5357

AN:

1451106

Hom.:

Cov.:

AF XY:

0.00339

AC XY:

2443

AN XY:

720914

show subpopulations

African (AFR)

AF:

0.0670

AC:

2201

AN:

32840

American (AMR)

AF:

0.00594

AC:

261

AN:

43906

Ashkenazi Jewish (ASJ)

AF:

0.0114

AC:

293

AN:

25738

East Asian (EAS)

AF:

0.000809

AC:

AN:

39536

South Asian (SAS)

AF:

0.000891

AC:

AN:

85284

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

53078

Middle Eastern (MID)

AF:

0.0178

AC:

AN:

5452

European-Non Finnish (NFE)

AF:

0.00174

AC:

1919

AN:

1105374

Other (OTH)

AF:

0.00790

AC:

473

AN:

59898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

245

491

736

982

1227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

232

348

464

580

<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

AF:

0.0188

AC:

2707

AN:

144310

Hom.:

Cov.:

AF XY:

0.0181

AC XY:

1264

AN XY:

69874

show subpopulations

African (AFR)

AF:

0.0595

AC:

2269

AN:

38160

American (AMR)

AF:

0.0124

AC:

175

AN:

14158

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

AN:

3402

East Asian (EAS)

AF:

0.00119

AC:

AN:

5038

South Asian (SAS)

AF:

0.00213

AC:

AN:

4224

European-Finnish (FIN)

AF:

0.000104

AC:

AN:

9648

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00249

AC:

166

AN:

66550

Other (OTH)

AF:

0.0201

AC:

AN:

1940

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

110

220

330

440

550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00315

Hom.:

Bravo

AF:

0.0238

ESP6500AA

AF:

0.0660

AC:

264

ESP6500EA

AF:

0.00304

AC:

ExAC

AF:

0.00746

AC:

902

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.8

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.029

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.26

MetaRNN

Benign

0.0036

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.28

PhyloP100

0.44

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.58

REVEL

Benign

0.0050

Sift

Benign

0.13

Sift4G

Benign

0.23

Polyphen

0.0020

Vest4

0.051

MVP

0.043

MPC

1.4

ClinPred

0.0016

GERP RS

0.51

PromoterAI

-0.026

Neutral

(source)

Varity_R

0.098

gMVP

0.024

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over