chr1-61088233-C-T
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001134673.4(NFIA):c.112C>T(p.Arg38*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
NFIA
NM_001134673.4 stop_gained
NM_001134673.4 stop_gained
Scores
4
2
Clinical Significance
Conservation
PhyloP100: 2.12
Publications
0 publications found
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 defectsInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
- chromosome 1p32-p31 deletion syndromeInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-61088233-C-T is Pathogenic according to our data. Variant chr1-61088233-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 520757.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001134673.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NFIA | NM_001134673.4 | MANE Select | c.112C>T | p.Arg38* | stop_gained | Exon 2 of 11 | NP_001128145.1 | Q12857-1 | |
| NFIA | NM_001145512.2 | c.247C>T | p.Arg83* | stop_gained | Exon 3 of 12 | NP_001138984.1 | Q12857-4 | ||
| NFIA | NM_001145511.2 | c.88C>T | p.Arg30* | stop_gained | Exon 2 of 11 | NP_001138983.1 | Q12857-3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NFIA | ENST00000403491.8 | TSL:1 MANE Select | c.112C>T | p.Arg38* | stop_gained | Exon 2 of 11 | ENSP00000384523.3 | Q12857-1 | |
| NFIA | ENST00000371187.7 | TSL:1 | c.112C>T | p.Arg38* | stop_gained | Exon 2 of 10 | ENSP00000360229.3 | Q12857-2 | |
| NFIA | ENST00000476646.5 | TSL:3 | c.-30C>T | 5_prime_UTR_premature_start_codon_gain | Exon 2 of 4 | ENSP00000474461.1 | S4R3K4 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461840Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727208 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
2
AN:
1461840
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
727208
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33476
American (AMR)
AF:
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26132
East Asian (EAS)
AF:
AC:
1
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53402
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111988
Other (OTH)
AF:
AC:
0
AN:
60396
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0448430), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.350
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
GnomAD4 genome
Cov.:
31
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Conflicting classifications of pathogenicity
Revision:criteria provided, conflicting classifications
Pathogenic
VUS
Benign
Condition
1
-
-
Brain malformations with or without urinary tract defects (1)
-
1
-
Inborn genetic diseases (1)
1
-
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
PhyloP100
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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
Publications
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