15-83257510-G-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PVS1_ModerateBS2
The NM_001717.4(BNC1):c.2917C>T(p.Arg973*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,614,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
BNC1
NM_001717.4 stop_gained
NM_001717.4 stop_gained
Scores
2
4
1
Clinical Significance
Conservation
PhyloP100: 3.11
Genes affected
BNC1 (HGNC:1081): (basonuclin zinc finger protein 1) This gene encodes a zinc finger protein present in the basal cell layer of the epidermis and in hair follicles. It is also found in abundance in the germ cells of testis and ovary. This protein is thought to play a regulatory role in keratinocyte proliferation and it may also be a regulator for rRNA transcription. Disruption of this gene has been implicated in premature ovarian failure as well as testicular premature aging. [provided by RefSeq, Sep 2020]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0228 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
BS2
High AC in GnomAdExome4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BNC1 | NM_001717.4 | c.2917C>T | p.Arg973* | stop_gained | 5/5 | ENST00000345382.7 | NP_001708.3 | |
BNC1 | NM_001301206.2 | c.2896C>T | p.Arg966* | stop_gained | 5/5 | NP_001288135.1 | ||
BNC1 | XM_011521893.2 | c.2842C>T | p.Arg948* | stop_gained | 5/5 | XP_011520195.1 | ||
BNC1 | XM_011521894.1 | c.2563C>T | p.Arg855* | stop_gained | 4/4 | XP_011520196.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BNC1 | ENST00000345382.7 | c.2917C>T | p.Arg973* | stop_gained | 5/5 | 1 | NM_001717.4 | ENSP00000307041.2 | ||
BNC1 | ENST00000569704.2 | c.2896C>T | p.Arg966* | stop_gained | 5/5 | 5 | ENSP00000456727.1 | |||
ENSG00000259986 | ENST00000565495.1 | n.264+72442G>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152136Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251322Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135822
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461868Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727238
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152136Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74318
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Premature ovarian failure 16 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Feb 16, 2020 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
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Uncertain
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Uncertain
FATHMM_MKL
Uncertain
D
Vest4
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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