Variant 9-14116313-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001190737.2(NFIB):c.1279C>T(p.Pro427Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000029 in 1,381,676 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

NFIB
NM_001190737.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.23

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFIB	NM_001190737.2 link	c.1279C>T	p.Pro427Ser	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.1279C>T	p.Pro427Ser	missense_variant	9/11	1	NM_001190737.2	ENSP00000370340.1		O00712-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000146

AC:

AN:

137286

Hom.:

AF XY:

0.0000136

AC XY:

AN XY:

73690

show subpopulations

Gnomad AFR exome

AF:

0.000306

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000290

AC:

AN:

1381676

Hom.:

Cov.:

AF XY:

0.00000441

AC XY:

AN XY:

680906

show subpopulations

Gnomad4 AFR exome

AF:

0.0000644

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000285

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.34e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 09, 2024

The c.1279C>T (p.P427S) alteration is located in exon 9 (coding exon 9) of the NFIB gene. This alteration results from a C to T substitution at nucleotide position 1279, causing the proline (P) at amino acid position 427 to be replaced by a serine (S). Based on data from gnomAD, the T allele has an overall frequency of 0.002% (2/137286) total alleles studied. The highest observed frequency was 0.031% (2/6538) of African alleles. This amino acid position is highly conserved in available vertebrate species. The in silico prediction for this alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

.;.;T;T;.;T

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.94

D;D;D;D;D;D

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.47

T;T;T;T;T;T

MetaSVM

Benign

-0.99

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-2.1

N;N;N;N;.;.

REVEL

Uncertain

0.33

Sift

Benign

0.11

T;T;T;T;.;.

Sift4G

Benign

0.18

T;T;T;T;.;.

Vest4

0.84

MutPred

0.42

.;Gain of glycosylation at P427 (P = 0.0146);Gain of glycosylation at P427 (P = 0.0146);Gain of glycosylation at P427 (P = 0.0146);.;.;

MVP

0.13

MPC

1.5

ClinPred

0.37

GERP RS

5.9

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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