1-61082762-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001134673.4(NFIA):​c.-30C>A variant causes a 5 prime UTR change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 28)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

NFIA
NM_001134673.4 5_prime_UTR

Scores

1
15
Splicing: ADA: 0.003580
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.39
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10633552).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NFIANM_001134673.4 linkuse as main transcriptc.-30C>A 5_prime_UTR_variant 1/11 ENST00000403491.8 NP_001128145.1
NFIANM_001145512.2 linkuse as main transcriptc.106C>A p.Arg36Ser missense_variant, splice_region_variant 2/12 NP_001138984.1
NFIANM_005595.5 linkuse as main transcriptc.-30C>A 5_prime_UTR_variant 1/10 NP_005586.1
NFIANM_001145511.2 linkuse as main transcriptc.3+5134C>A intron_variant NP_001138983.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NFIAENST00000403491.8 linkuse as main transcriptc.-30C>A 5_prime_UTR_variant 1/111 NM_001134673.4 ENSP00000384523 P1Q12857-1

Frequencies

GnomAD3 genomes
Cov.:
28
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1401092
Hom.:
0
Cov.:
39
AF XY:
0.00
AC XY:
0
AN XY:
691304
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
28
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxDec 15, 2022Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Reported using an alternate transcript of the gene -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
20
DANN
Benign
0.95
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.31
FATHMM_MKL
Benign
0.48
N
LIST_S2
Benign
0.44
T
M_CAP
Benign
0.044
D
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;N
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
0.29
N
REVEL
Benign
0.11
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Vest4
0.30
MutPred
0.13
Gain of glycosylation at R36 (P = 0.0035);
MVP
0.45
MPC
0.93
ClinPred
0.35
T
GERP RS
2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
gMVP
0.38

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0036
dbscSNV1_RF
Benign
0.076
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs937674643; hg19: chr1-61548434; API