9-91447930-C-T

Variant names:

• chr9-91447930-C-T
• rs4744045
• XM_047423425.1:c.-173+35417G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047423425.1(NFIL3):​c.-173+35417G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 151,982 control chromosomes in the GnomAD database, including 19,305 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 0.45 (19305 hom., cov: 32)
• Consequence: NFIL3 XM_047423425.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFIL3	XM_047423425.1	c.-173+35417G>A		intron_variant	Intron 1 of 1		XP_047279381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68409 AN: 151864 Hom.: 19255 Cov.: 32

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.451 AC: 68512 AN: 151982 Hom.: 19305 Cov.: 32 AF XY: 0.451 AC XY: 33525 AN XY: 74268

African (AFR) AF: 0.790 AC: 32785 AN: 41498

American (AMR) AF: 0.302 AC: 4602 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1309 AN: 3470

East Asian (EAS) AF: 0.662 AC: 3416 AN: 5164

South Asian (SAS) AF: 0.427 AC: 2059 AN: 4822

European-Finnish (FIN) AF: 0.351 AC: 3692 AN: 10518

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19364 AN: 67952

Other (OTH) AF: 0.434 AC: 915 AN: 2106

Alfa AF: 0.353 Hom.: 8614

Bravo AF: 0.465

Asia WGS AF: 0.575 AC: 1997 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.93
DANN	Benign	0.30
PhyloP100		-1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4744045; hg19: chr9-94210212; COSMIC: COSV60377947;