9-16419312-T-C
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_017637.6(BNC2):c.2977A>G(p.Ile993Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000049 in 1,613,702 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000052 ( 2 hom. )
Consequence
BNC2
NM_017637.6 missense
NM_017637.6 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: 1.63
Genes affected
BNC2 (HGNC:30988): (basonuclin zinc finger protein 2) This gene encodes a conserved zinc finger protein. The encoded protein functions in skin color saturation. Mutations in this gene are associated with facial pigmented spots. This gene is also associated with susceptibility to adolescent idiopathic scoliosis. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.010811627).
BS2
?
High AC in GnomAdExome at 35 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BNC2 | NM_017637.6 | c.2977A>G | p.Ile993Val | missense_variant | 7/7 | ENST00000380672.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BNC2 | ENST00000380672.9 | c.2977A>G | p.Ile993Val | missense_variant | 7/7 | 2 | NM_017637.6 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152154Hom.: 0 Cov.: 31
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000140 AC: 35AN: 250892Hom.: 1 AF XY: 0.000140 AC XY: 19AN XY: 135570
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GnomAD4 exome AF: 0.0000520 AC: 76AN: 1461430Hom.: 2 Cov.: 35 AF XY: 0.0000702 AC XY: 51AN XY: 726964
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152272Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3AN XY: 74432
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 17, 2023 | The c.2977A>G (p.I993V) alteration is located in exon 7 (coding exon 7) of the BNC2 gene. This alteration results from a A to G substitution at nucleotide position 2977, causing the isoleucine (I) at amino acid position 993 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MutPred
Gain of relative solvent accessibility (P = 0.1259);.;
MVP
MPC
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