chr5-93585037-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4BP6
The NM_005654.6(NR2F1):c.14T>C(p.Val5Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000389 in 1,027,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000021 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000011 ( 0 hom. )
Consequence
NR2F1
NM_005654.6 missense
NM_005654.6 missense
Scores
2
3
9
Clinical Significance
Conservation
PhyloP100: 1.69
Genes affected
NR2F1 (HGNC:7975): (nuclear receptor subfamily 2 group F member 1) The protein encoded by this gene is a nuclear hormone receptor and transcriptional regulator. The encoded protein acts as a homodimer and binds to 5'-AGGTCA-3' repeats. Defects in this gene are a cause of Bosch-Boonstra optic atrophy syndrome (BBOAS). [provided by RefSeq, Apr 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, NR2F1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.32285988).
BP6
?
Variant 5-93585037-T-C is Benign according to our data. Variant chr5-93585037-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2194431.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NR2F1 | NM_005654.6 | c.14T>C | p.Val5Ala | missense_variant | 1/3 | ENST00000327111.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NR2F1 | ENST00000327111.8 | c.14T>C | p.Val5Ala | missense_variant | 1/3 | 1 | NM_005654.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000206 AC: 3AN: 145428Hom.: 0 Cov.: 30
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GnomAD4 exome AF: 0.00000113 AC: 1AN: 882460Hom.: 0 Cov.: 30 AF XY: 0.00000241 AC XY: 1AN XY: 415312
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GnomAD4 genome ? AF: 0.0000206 AC: 3AN: 145428Hom.: 0 Cov.: 30 AF XY: 0.0000283 AC XY: 2AN XY: 70700
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 12, 2021 | The c.14T>C (p.V5A) alteration is located in exon 1 (coding exon 1) of the NR2F1 gene. This alteration results from a T to C substitution at nucleotide position 14, causing the valine (V) at amino acid position 5 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
N;N;.;.
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
Polyphen
B;B;.;.
Vest4
0.40, 0.25
MutPred
Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);
MVP
0.92
ClinPred
T
GERP RS
Varity_R
gMVP
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