rs10991925

chr9-91415358-T-Cchr9-91415358-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005384.3(NFIL3):c.-172-4452A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,120 control chromosomes in the GnomAD database, including 7,442 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (7442 hom., cov: 32)
• Consequence: NFIL3 NM_005384.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.633

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFIL3	NM_005384.3	c.-172-4452A>G		intron_variant		ENST00000297689.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFIL3	ENST00000297689.4	c.-172-4452A>G		intron_variant		1	NM_005384.3	P1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46432 AN: 152002 Hom.: 7440 Cov.: 32

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.324

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.305 AC: 46458 AN: 152120 Hom.: 7442 Cov.: 32 AF XY: 0.302 AC XY: 22470 AN XY: 74350

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.325

Alfa AF: 0.282 Hom.: 1496

Bravo AF: 0.318

Asia WGS AF: 0.283 AC: 988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.5
Dann	Benign	0.44

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: rs10991925; hg19: chr9-94177640;