Genetic Variant IFNE:p.Gln46His (chr9-21481557-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_176891.5(IFNE):c.138A>C(p.Gln46His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0689 in 1,613,856 control chromosomes in the GnomAD database, including 4,211 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.061 ( 313 hom., cov: 33)

Exomes 𝑓: 0.070 ( 3898 hom. )

Consequence

IFNE
NM_176891.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.22

Publications

24 publications found

Variant links:

Genes affected

IFNE (HGNC:18163): (interferon epsilon) Predicted to enable cytokine activity and type I interferon receptor binding activity. Predicted to be involved in several processes, including B cell activation; defense response to other organism; and lymphocyte activation involved in immune response. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

IFNE 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001611799).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNE	NM_176891.5 link	c.138A>C	p.Gln46His	missense_variant	Exon 1 of 1	ENST00000448696.4	NP_795372.1	Q86WN2A0A7R8GUQ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNE	ENST00000448696.4 link	c.138A>C	p.Gln46His	missense_variant	Exon 1 of 1	6	NM_176891.5	ENSP00000418018.2		Q86WN2

Frequencies

GnomAD3 genomes

AF:

0.0614

AC:

9346

AN:

152184

Hom.:

315

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0408

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0885

Gnomad ASJ

AF:

0.0426

Gnomad EAS

AF:

0.0229

Gnomad SAS

AF:

0.0711

Gnomad FIN

AF:

0.0747

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0702

Gnomad OTH

AF:

0.0420

GnomAD2 exomes

AF:

0.0718

AC:

17957

AN:

250206

AF XY:

0.0696

show subpopulations

Gnomad AFR exome

AF:

0.0392

Gnomad AMR exome

AF:

0.133

Gnomad ASJ exome

AF:

0.0362

Gnomad EAS exome

AF:

0.0196

Gnomad FIN exome

AF:

0.0739

Gnomad NFE exome

AF:

0.0696

Gnomad OTH exome

AF:

0.0628

GnomAD4 exome

AF:

0.0697

AC:

101883

AN:

1461554

Hom.:

3898

Cov.:

AF XY:

0.0693

AC XY:

50374

AN XY:

727080

show subpopulations

African (AFR)

AF:

0.0414

AC:

1386

AN:

33476

American (AMR)

AF:

0.125

AC:

5602

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0382

AC:

997

AN:

26132

East Asian (EAS)

AF:

0.0160

AC:

634

AN:

39694

South Asian (SAS)

AF:

0.0722

AC:

6230

AN:

86246

European-Finnish (FIN)

AF:

0.0801

AC:

4277

AN:

53368

Middle Eastern (MID)

AF:

0.0382

AC:

220

AN:

5766

European-Non Finnish (NFE)

AF:

0.0708

AC:

78760

AN:

1111756

Other (OTH)

AF:

0.0625

AC:

3777

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

5167

10334

15501

20668

25835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2958

5916

8874

11832

14790

<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:

0.0614

AC:

9348

AN:

152302

Hom.:

313

Cov.:

AF XY:

0.0615

AC XY:

4580

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0407

AC:

1690

AN:

41560

American (AMR)

AF:

0.0884

AC:

1353

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0426

AC:

148

AN:

3472

East Asian (EAS)

AF:

0.0230

AC:

119

AN:

5182

South Asian (SAS)

AF:

0.0716

AC:

346

AN:

4832

European-Finnish (FIN)

AF:

0.0747

AC:

793

AN:

10614

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0702

AC:

4778

AN:

68018

Other (OTH)

AF:

0.0416

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

434

868

1301

1735

2169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0651

Hom.:

1564

Bravo

AF:

0.0617

TwinsUK

AF:

0.0680

AC:

252

ALSPAC

AF:

0.0703

AC:

271

ESP6500AA

AF:

0.0381

AC:

168

ESP6500EA

AF:

0.0703

AC:

605

ExAC

AF:

0.0697

AC:

8463

Asia WGS

AF:

0.0490

AC:

171

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.3

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0033

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.47

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.6

PhyloP100

-3.2

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.98

REVEL

Benign

0.048

Sift

Benign

0.11

Sift4G

Benign

0.11

Polyphen

0.071

Vest4

0.031

MutPred

0.14

Gain of catalytic residue at L48 (P = 0.0637);

MPC

0.015

ClinPred

0.013

GERP RS

-8.9

Varity_R

0.14

gMVP

0.20

Mutation Taster

=96/4

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over