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
NM_001134673.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.924
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]
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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 |
---|---|---|---|---|---|---|---|---|
NFIA | NM_001134673.4 | c.1413G>A | p.Thr471= | synonymous_variant | 9/11 | ENST00000403491.8 | NP_001128145.1 | |
NFIA | NM_001145512.2 | c.1548G>A | p.Thr516= | synonymous_variant | 10/12 | NP_001138984.1 | ||
NFIA | NM_001145511.2 | c.1389G>A | p.Thr463= | synonymous_variant | 9/11 | NP_001138983.1 | ||
NFIA | NM_005595.5 | c.1413G>A | p.Thr471= | synonymous_variant | 9/10 | NP_005586.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NFIA | ENST00000403491.8 | c.1413G>A | p.Thr471= | synonymous_variant | 9/11 | 1 | NM_001134673.4 | ENSP00000384523 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000204 AC: 31AN: 152104Hom.: 1 Cov.: 30
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GnomAD3 exomes AF: 0.000184 AC: 44AN: 238554Hom.: 0 AF XY: 0.000225 AC XY: 29AN XY: 128742
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GnomAD4 exome AF: 0.000212 AC: 309AN: 1455548Hom.: 1 Cov.: 36 AF XY: 0.000242 AC XY: 175AN XY: 723472
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GnomAD4 genome AF: 0.000204 AC: 31AN: 152222Hom.: 1 Cov.: 30 AF XY: 0.000161 AC XY: 12AN XY: 74422
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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 submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | NFIA: BP4, BP7 - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 17, 2023 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 05, 2016 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at