9-91410710-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005384.3(NFIL3):c.25G>A(p.Val9Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,597,652 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (43 hom.)
• Consequence: NFIL3 NM_005384.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.05

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020663738).
• BP6: Variant 9-91410710-C-T is Benign according to our data. Variant chr9-91410710-C-T is described in ClinVar as [Benign]. Clinvar id is 720738.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00199 (303/152308) while in subpopulation AMR AF= 0.0169 (258/15300). AF 95% confidence interval is 0.0152. There are 4 homozygotes in gnomad4. There are 160 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 303 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFIL3	NM_005384.3	c.25G>A	p.Val9Ile	missense_variant	2/2	ENST00000297689.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFIL3	ENST00000297689.4	c.25G>A	p.Val9Ile	missense_variant	2/2	1	NM_005384.3	P1

Frequencies

GnomAD3 genomes AF: 0.00199 AC: 303 AN: 152190 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00568 AC: 1340 AN: 235968 Hom.: 34 AF XY: 0.00418 AC XY: 534 AN XY: 127746

Gnomad AFR exome AF: 0.000700

Gnomad AMR exome AF: 0.0417

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000582

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000552

Gnomad OTH exome AF: 0.00424

GnomAD4 exome AF: 0.00124 AC: 1789 AN: 1445344 Hom.: 43 Cov.: 31 AF XY: 0.00104 AC XY: 748 AN XY: 718228

Gnomad4 AFR exome AF: 0.000711

Gnomad4 AMR exome AF: 0.0398

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.000431

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000371

Gnomad4 OTH exome AF: 0.00131

GnomAD4 genome AF: 0.00199 AC: 303 AN: 152308 Hom.: 4 Cov.: 33 AF XY: 0.00215 AC XY: 160 AN XY: 74484

Gnomad4 AFR AF: 0.000698

Gnomad4 AMR AF: 0.0169

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.000315 Hom.: 2

Bravo AF: 0.00441

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00427 AC: 518

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 07, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	6.5
Dann	Benign	0.59
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.3	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.24	N
REVEL	Benign	0.043
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.071
MVP		0.043
MPC		0.35
ClinPred		0.0053	T
GERP RS		-0.27
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.039
gMVP		0.098

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: rs146293258; hg19: chr9-94172992; COSMIC: COSV52684457;