20-17531193-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001195.5(BFSP1):c.137G>C(p.Gly46Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,304,188 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0091 ( 25 hom., cov: 33)

Exomes 𝑓: 0.00073 ( 12 hom. )

Consequence

BFSP1
NM_001195.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.83

Variant links:

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]

BFSP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009263337).

BP6

Variant 20-17531193-C-G is Benign according to our data. Variant chr20-17531193-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 474089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00911 (1381/151604) while in subpopulation AFR AF= 0.0308 (1276/41460). AF 95% confidence interval is 0.0294. There are 25 homozygotes in gnomad4. There are 624 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 25 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BFSP1	NM_001195.5 link	c.137G>C	p.Gly46Ala	missense_variant	Exon 1 of 8	ENST00000377873.8	NP_001186.1	Q12934-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BFSP1	ENST00000377873.8 link	c.137G>C	p.Gly46Ala	missense_variant	Exon 1 of 8	1	NM_001195.5	ENSP00000367104.3	Q12934-1
BFSP1	ENST00000377868.6 link	c.3-6285G>C		intron_variant	Intron 1 of 7	1		ENSP00000367099.2	Q12934-2
BFSP1	ENST00000536626.7 link	c.-40-6285G>C		intron_variant	Intron 2 of 8	2		ENSP00000442522.1	Q12934-3
BFSP1	ENST00000473415.1 link	n.472-6285G>C		intron_variant	Intron 4 of 6	3

Frequencies

GnomAD3 genomes

AF:

0.00912

AC:

1381

AN:

151496

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0309

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00553

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00864

GnomAD3 exomes

AF:

0.000662

AC:

AN:

13596

Hom.:

AF XY:

0.000604

AC XY:

AN XY:

8272

show subpopulations

Gnomad AFR exome

AF:

0.0214

Gnomad AMR exome

AF:

0.000854

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00224

GnomAD4 exome

AF:

0.000729

AC:

840

AN:

1152584

Hom.:

Cov.:

AF XY:

0.000642

AC XY:

358

AN XY:

557980

show subpopulations

Gnomad4 AFR exome

AF:

0.0320

Gnomad4 AMR exome

AF:

0.00175

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000239

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000167

Gnomad4 OTH exome

AF:

0.00137

GnomAD4 genome

AF:

0.00911

AC:

1381

AN:

151604

Hom.:

Cov.:

AF XY:

0.00842

AC XY:

624

AN XY:

74122

show subpopulations

Gnomad4 AFR

AF:

0.0308

Gnomad4 AMR

AF:

0.00553

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00855

Alfa

AF:

0.00680

Hom.:

Bravo

AF:

0.0104

ExAC

AF:

0.0000984

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 16, 2024

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

Cataract 33

Benign:1

Nov 26, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.40

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0093

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.69

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.96

REVEL

Benign

0.19

Sift

Benign

0.86

Sift4G

Benign

0.82

Polyphen

0.034

Vest4

0.15

MVP

0.73

MPC

1.3

ClinPred

0.016

GERP RS

1.6

Varity_R

0.040

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over