chr3-133448607-AAAG-A
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PM2PM4_SupportingPP5_Very_Strong
The NM_003571.4(BFSP2):c.697_699delGAA(p.Glu233del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.000000684 in 1,461,744 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
BFSP2
NM_003571.4 conservative_inframe_deletion
NM_003571.4 conservative_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.79
Publications
6 publications found
Genes affected
BFSP2 (HGNC:1041): (beaded filament structural protein 2) More than 99% of the vertebrate ocular lens is comprised of terminally differentiated lens fiber cells. Two lens-specific intermediate filament-like proteins, the protein product of this gene (phakinin), and filensin, are expressed only after fiber cell differentiation has begun. Both proteins are found in a structurally unique cytoskeletal element that is referred to as the beaded filament (BF). Mutations in this gene have been associated with juvenile-onset, progressive cataracts and Dowling-Meara epidermolysis bullosa simplex. [provided by RefSeq, Jun 2009]
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_003571.4. Strenght limited to Supporting due to length of the change: 1aa.
PP5
Variant 3-133448607-AAAG-A is Pathogenic according to our data. Variant chr3-133448607-AAAG-A is described in ClinVar as Pathogenic. ClinVar VariationId is 6584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_003571.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| BFSP2 | NM_003571.4 | MANE Select | c.697_699delGAA | p.Glu233del | conservative_inframe_deletion | Exon 3 of 7 | NP_003562.1 | ||
| BFSP2-AS1 | NR_135276.2 | n.458+171_458+173delCTT | intron | N/A | |||||
| BFSP2-AS1 | NR_135277.2 | n.344-3035_344-3033delCTT | intron | N/A |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| BFSP2 | ENST00000302334.3 | TSL:1 MANE Select | c.697_699delGAA | p.Glu233del | conservative_inframe_deletion | Exon 3 of 7 | ENSP00000304987.2 | ||
| BFSP2-AS1 | ENST00000515542.1 | TSL:1 | n.282+171_282+173delCTT | intron | N/A | ||||
| BFSP2-AS1 | ENST00000833670.1 | n.484_486delCTT | non_coding_transcript_exon | Exon 2 of 2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000399 AC: 1AN: 250540 AF XY: 0.00000738 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
250540
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461744Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727160 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461744
Hom.:
AF XY:
AC XY:
1
AN XY:
727160
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33478
American (AMR)
AF:
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26134
East Asian (EAS)
AF:
AC:
0
AN:
39696
South Asian (SAS)
AF:
AC:
0
AN:
86230
European-Finnish (FIN)
AF:
AC:
0
AN:
53400
Middle Eastern (MID)
AF:
AC:
0
AN:
5750
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111950
Other (OTH)
AF:
AC:
0
AN:
60386
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
2
-
-
Cataract 12 multiple types (2)
1
-
-
BFSP2-related disorder (1)
1
-
-
not provided (2)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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