Variant 9-91410225-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005384.3(NFIL3):c.510G>A(p.Met170Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00313 in 1,614,056 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 5 hom. )

Consequence

NFIL3
NM_005384.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter U:1B:1

Conservation

PhyloP100: -0.0340

Variant links:

Genes affected

NFIL3 (HGNC:7787): (nuclear factor, interleukin 3 regulated) The protein encoded by this gene is a transcriptional regulator that binds as a homodimer to activating transcription factor (ATF) sites in many cellular and viral promoters. The encoded protein represses PER1 and PER2 expression and therefore plays a role in the regulation of circadian rhythm. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Feb 2014]

NFIL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055155754).

BP6

Variant 9-91410225-C-T is Benign according to our data. Variant chr9-91410225-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1693511.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 371 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFIL3	NM_005384.3 linkuse as main transcript	c.510G>A	p.Met170Ile	missense_variant	2/2	ENST00000297689.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFIL3	ENST00000297689.4 linkuse as main transcript	c.510G>A	p.Met170Ile	missense_variant	2/2	1	NM_005384.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00244

AC:

371

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00398

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00218

AC:

547

AN:

251358

Hom.:

AF XY:

0.00207

AC XY:

281

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00229

Gnomad ASJ exome

AF:

0.000893

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.00366

Gnomad OTH exome

AF:

0.00277

GnomAD4 exome

AF:

0.00321

AC:

4689

AN:

1461816

Hom.:

Cov.:

AF XY:

0.00312

AC XY:

2267

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.00246

Gnomad4 ASJ exome

AF:

0.00126

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000336

Gnomad4 FIN exome

AF:

0.000318

Gnomad4 NFE exome

AF:

0.00389

Gnomad4 OTH exome

AF:

0.00253

GnomAD4 genome

AF:

0.00244

AC:

371

AN:

152240

Hom.:

Cov.:

AF XY:

0.00208

AC XY:

155

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000795

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00398

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00353

Hom.:

Bravo

AF:

0.00251

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00465

AC:

ExAC

AF:

0.00227

AC:

276

EpiCase

AF:

0.00365

EpiControl

AF:

0.00397

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Jun 13, 2022

- -

NFIL3-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 22, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

Cadd

Benign

3.4

Dann

Benign

0.71

DEOGEN2

Benign

0.23

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.60

M_CAP

Benign

0.0056

MetaRNN

Benign

0.0055

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.77

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.92

REVEL

Benign

0.12

Sift

Benign

0.20

Sift4G

Benign

0.40

Polyphen

0.0

Vest4

0.12

MutPred

0.49

Gain of sheet (P = 0.0061);

MVP

0.043

MPC

0.48

ClinPred

0.0031

GERP RS

3.9

Varity_R

0.12

gMVP

0.18

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

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