Variant 9-91409346-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005384.3(NFIL3):c.1389A>G(p.Ter463Ter) variant causes a stop retained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000654 in 1,552,854 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00094 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00062 ( 11 hom. )

Consequence

NFIL3
NM_005384.3 stop_retained

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.49

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 9-91409346-T-C is Benign according to our data. Variant chr9-91409346-T-C is described in ClinVar as [Benign]. Clinvar id is 721540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.49 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000939 (143/152348) while in subpopulation EAS AF= 0.0222 (115/5190). AF 95% confidence interval is 0.0189. There are 2 homozygotes in gnomad4. There are 86 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 143 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFIL3	NM_005384.3 linkuse as main transcript	c.1389A>G	p.Ter463Ter	stop_retained_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.1389A>G	p.Ter463Ter	stop_retained_variant	2/2	1	NM_005384.3	ENSP00000297689.2		Q16649

Frequencies

GnomAD3 genomes

AF:

0.000953

AC:

145

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0223

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00224

AC:

454

AN:

202988

Hom.:

AF XY:

0.00205

AC XY:

222

AN XY:

108404

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000161

Gnomad ASJ exome

AF:

0.000176

Gnomad EAS exome

AF:

0.0232

Gnomad SAS exome

AF:

0.000102

Gnomad FIN exome

AF:

0.000636

Gnomad NFE exome

AF:

0.000361

Gnomad OTH exome

AF:

0.00296

GnomAD4 exome

AF:

0.000623

AC:

873

AN:

1400506

Hom.:

Cov.:

AF XY:

0.000597

AC XY:

413

AN XY:

691226

show subpopulations

Gnomad4 AFR exome

AF:

0.0000322

Gnomad4 AMR exome

AF:

0.000149

Gnomad4 ASJ exome

AF:

0.000227

Gnomad4 EAS exome

AF:

0.0146

Gnomad4 SAS exome

AF:

0.000225

Gnomad4 FIN exome

AF:

0.000760

Gnomad4 NFE exome

AF:

0.000134

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.000939

AC:

143

AN:

152348

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0222

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000270

Hom.:

Bravo

AF:

0.000899

Asia WGS

AF:

0.00953

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	Aug 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.0

DANN

Benign

0.60

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