Variant chr9-14116328-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001190737.2(NFIB):c.1264G>C(p.Val422Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00266 in 1,523,380 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 4 hom. )

Consequence

NFIB
NM_001190737.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 7.47

Variant links:

Genes affected

NFIB (HGNC:7785): (nuclear factor I B) Enables DNA-binding transcription activator activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and transcription regulator inhibitor activity. Involved in brain development; negative regulation of DNA binding activity; and regulation of transcription by RNA polymerase II. Located in fibrillar center and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NFIB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01411134).

BP6

Variant 9-14116328-C-G is Benign according to our data. Variant chr9-14116328-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2499087.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 267 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFIB	NM_001190737.2 link	c.1264G>C	p.Val422Leu	missense_variant	9/11	ENST00000380953.6	NP_001177666.1	O00712-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFIB	ENST00000380953.6 link	c.1264G>C	p.Val422Leu	missense_variant	9/11	1	NM_001190737.2	ENSP00000370340.1		O00712-5

Frequencies

GnomAD3 genomes

AF:

0.00175

AC:

267

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00344

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00156

AC:

198

AN:

126870

Hom.:

AF XY:

0.00141

AC XY:

AN XY:

67952

show subpopulations

Gnomad AFR exome

AF:

0.000157

Gnomad AMR exome

AF:

0.000106

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000687

Gnomad FIN exome

AF:

0.000621

Gnomad NFE exome

AF:

0.00348

Gnomad OTH exome

AF:

0.00140

GnomAD4 exome

AF:

0.00276

AC:

3780

AN:

1371058

Hom.:

Cov.:

AF XY:

0.00259

AC XY:

1751

AN XY:

674860

show subpopulations

Gnomad4 AFR exome

AF:

0.000554

Gnomad4 AMR exome

AF:

0.000192

Gnomad4 ASJ exome

AF:

0.0000419

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000555

Gnomad4 FIN exome

AF:

0.000879

Gnomad4 NFE exome

AF:

0.00334

Gnomad4 OTH exome

AF:

0.00186

GnomAD4 genome

AF:

0.00175

AC:

267

AN:

152322

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

118

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00344

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00240

Hom.:

Bravo

AF:

0.00169

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00441

AC:

ExAC

AF:

0.00119

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

NFIB-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

NFIB: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

.;.;T;T;.;T

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.82

T;T;T;T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.014

T;T;T;T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.19

N;N;N;N;.;.

REVEL

Benign

0.13

Sift

Benign

0.21

T;T;T;T;.;.

Sift4G

Benign

0.32

T;T;T;T;.;.

Vest4

0.45

MutPred

0.43

.;Loss of glycosylation at S419 (P = 0.1159);Loss of glycosylation at S419 (P = 0.1159);Loss of glycosylation at S419 (P = 0.1159);.;.;

MVP

0.13

MPC

1.1

ClinPred

0.053

GERP RS

5.0

gMVP

0.25

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over