chr9-14120480-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001190737.2(NFIB):c.1205A>G(p.Tyr402Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
NFIB
NM_001190737.2 missense
NM_001190737.2 missense
Scores
4
8
5
Clinical Significance
Conservation
PhyloP100: 7.31
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]
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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 | UniProt |
---|---|---|---|---|---|---|---|
NFIB | NM_001190737.2 | c.1205A>G | p.Tyr402Cys | missense_variant | 8/11 | ENST00000380953.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NFIB | ENST00000380953.6 | c.1205A>G | p.Tyr402Cys | missense_variant | 8/11 | 1 | NM_001190737.2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461864Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727232
GnomAD4 exome
AF:
AC:
1
AN:
1461864
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
727232
Gnomad4 AFR exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
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 | May 01, 2022 | The c.1205A>G (p.Y402C) alteration is located in exon 8 (coding exon 8) of the NFIB gene. This alteration results from a A to G substitution at nucleotide position 1205, causing the tyrosine (Y) at amino acid position 402 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;N;D;D;D;N;.;.;.;.;.;.;.;N;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;D;.;.;.;.;.;.;.;D;D
Sift4G
Benign
T;D;D;D;D;D;.;.;.;.;.;.;.;D;T
Polyphen
1.0
.;D;.;.;.;D;.;.;.;.;.;.;.;.;.
Vest4
MutPred
0.61
.;Loss of phosphorylation at Y402 (P = 0.0243);Loss of phosphorylation at Y402 (P = 0.0243);Loss of phosphorylation at Y402 (P = 0.0243);Loss of phosphorylation at Y402 (P = 0.0243);Loss of phosphorylation at Y402 (P = 0.0243);.;.;.;.;Loss of phosphorylation at Y402 (P = 0.0243);.;.;.;.;
MVP
MPC
2.2
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at