20-17494323-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001195.5(BFSP1):c.1749A>G(p.Pro583Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 1,614,018 control chromosomes in the GnomAD database, including 418,907 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P583P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.74 ( 41399 hom., cov: 33)

Exomes 𝑓: 0.72 ( 377508 hom. )

Consequence

BFSP1
NM_001195.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -5.31

Publications

24 publications found

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 Gene-Disease associations (from GenCC):

cataract 33
Inheritance: AR, AD, SD Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
early-onset nuclear cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

BFSP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 20-17494323-T-C is Benign according to our data. Variant chr20-17494323-T-C is described in ClinVar as [Benign]. Clinvar id is 257615.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BFSP1	NM_001195.5 link	c.1749A>G	p.Pro583Pro	synonymous_variant	Exon 8 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.1749A>G	p.Pro583Pro	synonymous_variant	Exon 8 of 8	1	NM_001195.5	ENSP00000367104.3	Q12934-1
BFSP1	ENST00000377868.6 link	c.1374A>G	p.Pro458Pro	synonymous_variant	Exon 8 of 8	1		ENSP00000367099.2	Q12934-2
BFSP1	ENST00000536626.7 link	c.1332A>G	p.Pro444Pro	synonymous_variant	Exon 9 of 9	2		ENSP00000442522.1	Q12934-3

Frequencies

GnomAD3 genomes

AF:

0.736

AC:

111949

AN:

152026

Hom.:

41366

Cov.:

show subpopulations

Gnomad AFR

AF:

0.790

Gnomad AMI

AF:

0.686

Gnomad AMR

AF:

0.774

Gnomad ASJ

AF:

0.757

Gnomad EAS

AF:

0.641

Gnomad SAS

AF:

0.790

Gnomad FIN

AF:

0.663

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.710

Gnomad OTH

AF:

0.743

GnomAD2 exomes

AF:

0.731

AC:

183735

AN:

251436

AF XY:

0.730

show subpopulations

Gnomad AFR exome

AF:

0.790

Gnomad AMR exome

AF:

0.810

Gnomad ASJ exome

AF:

0.762

Gnomad EAS exome

AF:

0.648

Gnomad FIN exome

AF:

0.658

Gnomad NFE exome

AF:

0.708

Gnomad OTH exome

AF:

0.717

GnomAD4 exome

AF:

0.718

AC:

1049259

AN:

1461876

Hom.:

377508

Cov.:

AF XY:

0.720

AC XY:

523291

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.791

AC:

26495

AN:

33480

American (AMR)

AF:

0.802

AC:

35857

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.758

AC:

19810

AN:

26136

East Asian (EAS)

AF:

0.610

AC:

24216

AN:

39700

South Asian (SAS)

AF:

0.789

AC:

68033

AN:

86258

European-Finnish (FIN)

AF:

0.658

AC:

35123

AN:

53404

Middle Eastern (MID)

AF:

0.723

AC:

4169

AN:

5768

European-Non Finnish (NFE)

AF:

0.712

AC:

792133

AN:

1112010

Other (OTH)

AF:

0.719

AC:

43423

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

20667

41335

62002

82670

103337

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.736

AC:

112035

AN:

152142

Hom.:

41399

Cov.:

AF XY:

0.735

AC XY:

54705

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.790

AC:

32767

AN:

41502

American (AMR)

AF:

0.774

AC:

11834

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.757

AC:

2630

AN:

3472

East Asian (EAS)

AF:

0.641

AC:

3305

AN:

5156

South Asian (SAS)

AF:

0.789

AC:

3809

AN:

4826

European-Finnish (FIN)

AF:

0.663

AC:

7028

AN:

10596

Middle Eastern (MID)

AF:

0.765

AC:

225

AN:

294

European-Non Finnish (NFE)

AF:

0.710

AC:

48253

AN:

67990

Other (OTH)

AF:

0.738

AC:

1558

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1550

3100

4650

6200

7750

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.721

Hom.:

71239

Bravo

AF:

0.748

EpiCase

AF:

0.712

EpiControl

AF:

0.714

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 24, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Cataract 33

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.045

(source)

DANN

Benign

0.39

PhyloP100

-5.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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20-17494323-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over