GeneBe

1-61406720-G-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001134673.4(NFIA):​c.1413G>C​(p.Thr471Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T471T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

NFIA
NM_001134673.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.924

Publications

1 publications found
Variant links:
Genes affected
NFIA (HGNC:7784): (nuclear factor I A) This gene encodes a member of the NF1 (nuclear factor 1) family of transcription factors. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
NFIA Gene-Disease associations (from GenCC):
  • brain malformations with or without urinary tract defects
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
  • chromosome 1p32-p31 deletion syndrome
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, Ambry Genetics

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.45).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NFIANM_001134673.4 linkc.1413G>C p.Thr471Thr synonymous_variant Exon 9 of 11 ENST00000403491.8 NP_001128145.1
NFIANM_001145512.2 linkc.1548G>C p.Thr516Thr synonymous_variant Exon 10 of 12 NP_001138984.1
NFIANM_001145511.2 linkc.1389G>C p.Thr463Thr synonymous_variant Exon 9 of 11 NP_001138983.1
NFIANM_005595.5 linkc.1413G>C p.Thr471Thr synonymous_variant Exon 9 of 10 NP_005586.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NFIAENST00000403491.8 linkc.1413G>C p.Thr471Thr synonymous_variant Exon 9 of 11 1 NM_001134673.4 ENSP00000384523.3

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1455548
Hom.:
0
Cov.:
36
AF XY:
0.00000138
AC XY:
1
AN XY:
723472
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33356
American (AMR)
AF:
0.00
AC:
0
AN:
43968
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25966
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39442
South Asian (SAS)
AF:
0.00
AC:
0
AN:
84668
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53116
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5754
European-Non Finnish (NFE)
AF:
9.02e-7
AC:
1
AN:
1109086
Other (OTH)
AF:
0.00
AC:
0
AN:
60192
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
30
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.45
CADD
Benign
12
DANN
Benign
0.65
PhyloP100
0.92
PromoterAI
-0.13
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Mutation Taster
=93/7
polymorphism

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

Other links and lift over

dbSNP: rs146012018; hg19: chr1-61872392; API