rs774227

Variant names:

• chr9-91431659-G-A
• rs774227
• XM_047423425.1:c.-172-20753C>T

Variant summary

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

The XM_047423425.1(NFIL3):​c.-172-20753C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 151,930 control chromosomes in the GnomAD database, including 28,994 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 0.57 (28994 hom., cov: 30)
• Consequence: NFIL3 XM_047423425.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.860
• Publications: 9 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFIL3	XM_047423425.1	c.-172-20753C>T		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: 0.574 AC: 87088 AN: 151812 Hom.: 28995 Cov.: 30

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.573 AC: 87101 AN: 151930 Hom.: 28994 Cov.: 30 AF XY: 0.578 AC XY: 42894 AN XY: 74250

African (AFR) AF: 0.216 AC: 8950 AN: 41438

American (AMR) AF: 0.699 AC: 10665 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2129 AN: 3470

East Asian (EAS) AF: 0.477 AC: 2461 AN: 5154

South Asian (SAS) AF: 0.574 AC: 2767 AN: 4820

European-Finnish (FIN) AF: 0.776 AC: 8189 AN: 10554

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.732 AC: 49714 AN: 67926

Other (OTH) AF: 0.604 AC: 1275 AN: 2110

Alfa AF: 0.664 Hom.: 53049

Bravo AF: 0.552

Asia WGS AF: 0.485 AC: 1687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.39
PhyloP100		0.86

Splicing

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

Other links and lift over

dbSNP: rs774227; hg19: chr9-94193941;