9-91409913-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_005384.3(NFIL3):c.822G>A(p.Thr274=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00401 in 1,613,862 control chromosomes in the GnomAD database, including 217 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (98 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (119 hom.)
• Consequence: NFIL3 NM_005384.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.76

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 9-91409913-C-T is Benign according to our data. Variant chr9-91409913-C-T is described in ClinVar as [Benign]. Clinvar id is 785289.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.76 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFIL3	NM_005384.3	c.822G>A	p.Thr274=	synonymous_variant	2/2	ENST00000297689.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFIL3	ENST00000297689.4	c.822G>A	p.Thr274=	synonymous_variant	2/2	1	NM_005384.3	P1

Frequencies

GnomAD3 genomes AF: 0.0213 AC: 3242 AN: 152014 Hom.: 98 Cov.: 32

Gnomad AFR AF: 0.0742

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00826

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0139

GnomAD3 exomes AF: 0.00577 AC: 1449 AN: 251330 Hom.: 45 AF XY: 0.00431 AC XY: 585 AN XY: 135836

Gnomad AFR exome AF: 0.0792

Gnomad AMR exome AF: 0.00370

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000294

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00221 AC: 3235 AN: 1461730 Hom.: 119 Cov.: 31 AF XY: 0.00194 AC XY: 1410 AN XY: 727184

Gnomad4 AFR exome AF: 0.0793

Gnomad4 AMR exome AF: 0.00441

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000278

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000692

Gnomad4 OTH exome AF: 0.00444

GnomAD4 genome AF: 0.0213 AC: 3244 AN: 152132 Hom.: 98 Cov.: 32 AF XY: 0.0202 AC XY: 1499 AN XY: 74372

Gnomad4 AFR AF: 0.0740

Gnomad4 AMR AF: 0.00824

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.00895 Hom.: 19

Bravo AF: 0.0246

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	0.10
Dann	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs35317894; hg19: chr9-94172195;