rs146012018

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001134673.4(NFIA):​c.1413G>A​(p.Thr471=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000211 in 1,607,770 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00020 ( 1 hom., cov: 30)
Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

NFIA
NM_001134673.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.924
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 Benign. Variant got -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
Variant 1-61406720-G-A is Benign according to our data. Variant chr1-61406720-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 435977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-61406720-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=0.924 with no splicing effect.
BS2
High AC in GnomAd4 at 31 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NFIANM_001134673.4 linkuse as main transcriptc.1413G>A p.Thr471= synonymous_variant 9/11 ENST00000403491.8 NP_001128145.1
NFIANM_001145512.2 linkuse as main transcriptc.1548G>A p.Thr516= synonymous_variant 10/12 NP_001138984.1
NFIANM_001145511.2 linkuse as main transcriptc.1389G>A p.Thr463= synonymous_variant 9/11 NP_001138983.1
NFIANM_005595.5 linkuse as main transcriptc.1413G>A p.Thr471= synonymous_variant 9/10 NP_005586.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NFIAENST00000403491.8 linkuse as main transcriptc.1413G>A p.Thr471= synonymous_variant 9/111 NM_001134673.4 ENSP00000384523 P1Q12857-1

Frequencies

GnomAD3 genomes
AF:
0.000204
AC:
31
AN:
152104
Hom.:
1
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.000279
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.000184
AC:
44
AN:
238554
Hom.:
0
AF XY:
0.000225
AC XY:
29
AN XY:
128742
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000911
Gnomad ASJ exome
AF:
0.000205
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000139
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000316
Gnomad OTH exome
AF:
0.000172
GnomAD4 exome
AF:
0.000212
AC:
309
AN:
1455548
Hom.:
1
Cov.:
36
AF XY:
0.000242
AC XY:
175
AN XY:
723472
show subpopulations
Gnomad4 AFR exome
AF:
0.0000600
Gnomad4 AMR exome
AF:
0.000250
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000165
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000175
Gnomad4 OTH exome
AF:
0.000482
GnomAD4 genome
AF:
0.000204
AC:
31
AN:
152222
Hom.:
1
Cov.:
30
AF XY:
0.000161
AC XY:
12
AN XY:
74422
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000279
Gnomad4 OTH
AF:
0.000947
Alfa
AF:
0.000225
Hom.:
0
Bravo
AF:
0.000200

ClinVar

Significance: Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:5
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMay 01, 2024NFIA: BP4, BP7 -
Likely benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 17, 2023- -
Likely benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, University Medical Center Utrecht-- -
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoOct 05, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.28
CADD
Benign
15
DANN
Benign
0.67
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs146012018; hg19: chr1-61872392; COSMIC: COSV63607773; COSMIC: COSV63607773; API