9-21440917-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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 0.019 ( 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

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 made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNA1	NM_024013.3 link	c.410C>T	p.Ala137Val	missense_variant	Exon 1 of 1	ENST00000276927.3	NP_076918.1	P01562L0N195

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNA1	ENST00000276927.3 link	c.410C>T	p.Ala137Val	missense_variant	Exon 1 of 1	6	NM_024013.3	ENSP00000276927.1		P01562

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

GnomAD3 exomes

AF:

0.00648

AC:

1556

AN:

240248

Hom.:

AF XY:

0.00528

AC XY:

689

AN XY:

130532

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 SAS exome

AF:

0.000887

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

Gnomad4 AFR exome

AF:

0.0670

Gnomad4 AMR exome

AF:

0.00594

Gnomad4 ASJ exome

AF:

0.0114

Gnomad4 EAS exome

AF:

0.000809

Gnomad4 SAS exome

AF:

0.000891

Gnomad4 FIN exome

AF:

0.0000942

Gnomad4 NFE exome

AF:

0.00174

Gnomad4 OTH exome

AF:

0.00790

GnomAD4 genome

AF:

0.0188

AC:

2707

AN:

144310

Hom.:

Cov.:

AF XY:

0.0181

AC XY:

1264

AN XY:

69874

show subpopulations

Gnomad4 AFR

AF:

0.0595

Gnomad4 AMR

AF:

0.0124

Gnomad4 ASJ

AF:

0.0112

Gnomad4 EAS

AF:

0.00119

Gnomad4 SAS

AF:

0.00213

Gnomad4 FIN

AF:

0.000104

Gnomad4 NFE

AF:

0.00249

Gnomad4 OTH

AF:

0.0201

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.8

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

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

Varity_R

0.098

gMVP

0.024

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

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