Variant chr9-91410710-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005384.3(NFIL3):c.25G>A(p.Val9Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,597,652 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 43 hom. )

Consequence

NFIL3
NM_005384.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.05

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020663738).

BP6

Variant 9-91410710-C-T is Benign according to our data. Variant chr9-91410710-C-T is described in ClinVar as [Benign]. Clinvar id is 720738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00199 (303/152308) while in subpopulation AMR AF= 0.0169 (258/15300). AF 95% confidence interval is 0.0152. There are 4 homozygotes in gnomad4. There are 160 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 303 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFIL3	NM_005384.3 linkuse as main transcript	c.25G>A	p.Val9Ile	missense_variant	2/2	ENST00000297689.4	NP_005375.2	Q16649A0A024R241

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFIL3	ENST00000297689.4 linkuse as main transcript	c.25G>A	p.Val9Ile	missense_variant	2/2	1	NM_005384.3	ENSP00000297689.2		Q16649

Frequencies

GnomAD3 genomes

AF:

0.00199

AC:

303

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0169

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00568

AC:

1340

AN:

235968

Hom.:

AF XY:

0.00418

AC XY:

534

AN XY:

127746

show subpopulations

Gnomad AFR exome

AF:

0.000700

Gnomad AMR exome

AF:

0.0417

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000582

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000552

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00124

AC:

1789

AN:

1445344

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

748

AN XY:

718228

show subpopulations

Gnomad4 AFR exome

AF:

0.000711

Gnomad4 AMR exome

AF:

0.0398

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000431

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000371

Gnomad4 OTH exome

AF:

0.00131

GnomAD4 genome

AF:

0.00199

AC:

303

AN:

152308

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

160

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.0169

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.000315

Hom.:

Bravo

AF:

0.00441

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00427

AC:

518

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.65

CADD

Benign

6.5

DANN

Benign

0.59

DEOGEN2

Benign

0.15

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0021

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.3

PrimateAI

Benign

0.34

PROVEAN

Benign

0.24

REVEL

Benign

0.043

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.071

MVP

0.043

MPC

0.35

ClinPred

0.0053

GERP RS

-0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.039

gMVP

0.098

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