Variant 9-21481499-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_176891.5(IFNE):c.196T>G(p.Ser66Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

IFNE
NM_176891.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.68

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.041529775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNE	NM_176891.5 link	c.196T>G	p.Ser66Ala	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.196T>G	p.Ser66Ala	missense_variant	Exon 1 of 1	6	NM_176891.5	ENSP00000418018.2		Q86WN2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461810

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.196T>G (p.S66A) alteration is located in exon 1 (coding exon 1) of the IFNE gene. This alteration results from a T to G substitution at nucleotide position 196, causing the serine (S) at amino acid position 66 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.8

DANN

Benign

0.53

DEOGEN2

Benign

0.0010

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.23

M_CAP

Benign

0.0075

MetaRNN

Benign

0.042

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.17

PrimateAI

Benign

0.32

PROVEAN

Benign

0.20

REVEL

Benign

0.0080

Sift

Benign

1.0

Sift4G

Benign

0.81

Polyphen

0.026

Vest4

0.043

MutPred

0.32

Loss of disorder (P = 0.0508);

MVP

0.27

MPC

0.016

ClinPred

0.034

GERP RS

-3.7

Varity_R

0.076

gMVP

0.037

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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