20-17496947-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001195.5(BFSP1):c.1033G>A(p.Gly345Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,533,522 control chromosomes in the GnomAD database, including 48,505 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3972 hom., cov: 32)

Exomes 𝑓: 0.25 ( 44533 hom. )

Consequence

BFSP1
NM_001195.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.631

Publications

32 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025340319).

BP6

Variant 20-17496947-C-T is Benign according to our data. Variant chr20-17496947-C-T is described in ClinVar as Benign. ClinVar VariationId is 257612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BFSP1	NM_001195.5 link	c.1033G>A	p.Gly345Ser	missense_variant	Exon 7 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.1033G>A	p.Gly345Ser	missense_variant	Exon 7 of 8	1	NM_001195.5	ENSP00000367104.3	Q12934-1
BFSP1	ENST00000377868.6 link	c.658G>A	p.Gly220Ser	missense_variant	Exon 7 of 8	1		ENSP00000367099.2	Q12934-2
BFSP1	ENST00000536626.7 link	c.616G>A	p.Gly206Ser	missense_variant	Exon 8 of 9	2		ENSP00000442522.1	Q12934-3

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32367

AN:

151702

Hom.:

3964

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0934

Gnomad AMI

AF:

0.145

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.264

Gnomad EAS

AF:

0.391

Gnomad SAS

AF:

0.358

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.246

Gnomad OTH

AF:

0.239

GnomAD2 exomes

AF:

0.263

AC:

37007

AN:

140546

AF XY:

0.269

show subpopulations

Gnomad AFR exome

AF:

0.0874

Gnomad AMR exome

AF:

0.309

Gnomad ASJ exome

AF:

0.268

Gnomad EAS exome

AF:

0.394

Gnomad FIN exome

AF:

0.220

Gnomad NFE exome

AF:

0.236

Gnomad OTH exome

AF:

0.254

GnomAD4 exome

AF:

0.249

AC:

343671

AN:

1381702

Hom.:

44533

Cov.:

AF XY:

0.252

AC XY:

172104

AN XY:

681624

show subpopulations

African (AFR)

AF:

0.0890

AC:

2710

AN:

30434

American (AMR)

AF:

0.304

AC:

9417

AN:

30946

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

6733

AN:

24786

East Asian (EAS)

AF:

0.390

AC:

13438

AN:

34456

South Asian (SAS)

AF:

0.350

AC:

26448

AN:

75600

European-Finnish (FIN)

AF:

0.223

AC:

10985

AN:

49182

Middle Eastern (MID)

AF:

0.257

AC:

1438

AN:

5604

European-Non Finnish (NFE)

AF:

0.240

AC:

257878

AN:

1073380

Other (OTH)

AF:

0.255

AC:

14624

AN:

57314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

11856

23711

35567

47422

59278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8910

17820

26730

35640

44550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.213

AC:

32394

AN:

151820

Hom.:

3972

Cov.:

AF XY:

0.217

AC XY:

16108

AN XY:

74196

show subpopulations

African (AFR)

AF:

0.0934

AC:

3868

AN:

41394

American (AMR)

AF:

0.273

AC:

4168

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

915

AN:

3468

East Asian (EAS)

AF:

0.391

AC:

2008

AN:

5140

South Asian (SAS)

AF:

0.360

AC:

1732

AN:

4810

European-Finnish (FIN)

AF:

0.221

AC:

2328

AN:

10548

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.246

AC:

16671

AN:

67902

Other (OTH)

AF:

0.238

AC:

501

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1242

2484

3725

4967

6209

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.239

Hom.:

15217

Bravo

AF:

0.209

TwinsUK

AF:

0.229

AC:

848

ALSPAC

AF:

0.247

AC:

952

ESP6500AA

AF:

0.0833

AC:

362

ESP6500EA

AF:

0.212

AC:

1781

ExAC

AF:

0.135

AC:

12081

Asia WGS

AF:

0.325

AC:

1132

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 02, 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

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 14, 2021

Genome-Nilou Lab

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

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.10

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.039

T;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0041

LIST_S2

Benign

0.53

T;T;T

MetaRNN

Benign

0.0025

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.17

N;.;.

PhyloP100

-0.63

PrimateAI

Benign

0.27

PROVEAN

Benign

0.79

N;N;N

REVEL

Benign

0.043

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.80

T;.;T

Polyphen

0.0010

B;B;.

Vest4

0.020

MPC

0.076

ClinPred

0.00012

GERP RS

-5.0

Varity_R

0.024

gMVP

0.15

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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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