rs557601555
Positions:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_001195.5(BFSP1):āc.776G>Cā(p.Cys259Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000694 in 1,614,188 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: š 0.000085 ( 0 hom., cov: 32)
Exomes š: 0.000068 ( 1 hom. )
Consequence
BFSP1
NM_001195.5 missense
NM_001195.5 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: 4.50
Genes affected
BFSP1 (HGNC:1040): (beaded filament structural protein 1) This gene encodes a lens-specific intermediate filament-like protein named filensin. The encoded protein is expressed in lens fiber cells after differentiation has begun. This protein functions as a component of the beaded filament which is a cytoskeletal structure found in lens fiber cells. Mutations in this gene are the cause of autosomal recessive cortical juvenile-onset cataract. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.013676822).
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000854 (13/152300) while in subpopulation SAS AF= 0.00269 (13/4828). AF 95% confidence interval is 0.00159. There are 0 homozygotes in gnomad4. There are 11 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BFSP1 | NM_001195.5 | c.776G>C | p.Cys259Ser | missense_variant | 6/8 | ENST00000377873.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BFSP1 | ENST00000377873.8 | c.776G>C | p.Cys259Ser | missense_variant | 6/8 | 1 | NM_001195.5 | P1 | |
BFSP1 | ENST00000377868.6 | c.401G>C | p.Cys134Ser | missense_variant | 6/8 | 1 | |||
BFSP1 | ENST00000536626.7 | c.359G>C | p.Cys120Ser | missense_variant | 7/9 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152182Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000135 AC: 34AN: 251468Hom.: 1 AF XY: 0.000177 AC XY: 24AN XY: 135912
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GnomAD4 exome AF: 0.0000677 AC: 99AN: 1461888Hom.: 1 Cov.: 32 AF XY: 0.0000921 AC XY: 67AN XY: 727244
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GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152300Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74482
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Congenital ocular coloboma Uncertain:1
Uncertain significance, no assertion criteria provided | research | Eye Genetics Research Group, Children's Medical Research Institute | Mar 30, 2012 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;D;D
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;.;T
Polyphen
B;B;.
Vest4
MutPred
Gain of disorder (P = 0.0133);.;.;
MVP
MPC
ClinPred
T
GERP RS
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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