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.

Variant Effect in Transcripts

 

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

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 v4.9

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;