9-91451720-T-C

Variant names:

• chr9-91451720-T-C
• rs1412470
• XM_047423425.1:c.-173+31627A>G

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+31627A>G 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 152,022 control chromosomes in the GnomAD database, including 19,316 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 (19316 hom., cov: 32)
• Consequence: NFIL3 XM_047423425.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.564
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFIL3	XM_047423425.1	c.-173+31627A>G		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: 68425 AN: 151904 Hom.: 19266 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: 0.350

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.451 AC: 68528 AN: 152022 Hom.: 19316 Cov.: 32 AF XY: 0.451 AC XY: 33520 AN XY: 74292

African (AFR) AF: 0.791 AC: 32786 AN: 41456

American (AMR) AF: 0.302 AC: 4611 AN: 15282

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

East Asian (EAS) AF: 0.661 AC: 3412 AN: 5162

South Asian (SAS) AF: 0.427 AC: 2060 AN: 4820

European-Finnish (FIN) AF: 0.350 AC: 3693 AN: 10564

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

European-Non Finnish (NFE) AF: 0.285 AC: 19372 AN: 67954

Other (OTH) AF: 0.434 AC: 914 AN: 2108

Alfa AF: 0.343 Hom.: 31553

Bravo AF: 0.465

Asia WGS AF: 0.577 AC: 2007 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.58
PhyloP100		-0.56

Splicing

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

Other links and lift over

dbSNP: rs1412470; hg19: chr9-94214002; COSMIC: COSV60378006;