chr20-17498972-G-A

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.804C>T(p.Asn268Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0709 in 1,614,044 control chromosomes in the GnomAD database, including 4,766 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 286 hom., cov: 32)

Exomes 𝑓: 0.073 ( 4480 hom. )

Consequence

BFSP1
NM_001195.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.64

Publications

8 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=-0.77).

BP6

Variant 20-17498972-G-A is Benign according to our data. Variant chr20-17498972-G-A is described in ClinVar as Benign. ClinVar VariationId is 257617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.64 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BFSP1	NM_001195.5 link	c.804C>T	p.Asn268Asn	synonymous_variant	Exon 6 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.804C>T	p.Asn268Asn	synonymous_variant	Exon 6 of 8	1	NM_001195.5	ENSP00000367104.3	Q12934-1
BFSP1	ENST00000377868.6 link	c.429C>T	p.Asn143Asn	synonymous_variant	Exon 6 of 8	1		ENSP00000367099.2	Q12934-2
BFSP1	ENST00000536626.7 link	c.387C>T	p.Asn129Asn	synonymous_variant	Exon 7 of 9	2		ENSP00000442522.1	Q12934-3

Frequencies

GnomAD3 genomes

AF:

0.0524

AC:

7975

AN:

152078

Hom.:

286

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0151

Gnomad AMI

AF:

0.0527

Gnomad AMR

AF:

0.0285

Gnomad ASJ

AF:

0.0418

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0228

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0796

Gnomad OTH

AF:

0.0463

GnomAD2 exomes

AF:

0.0551

AC:

13862

AN:

251466

AF XY:

0.0552

show subpopulations

Gnomad AFR exome

AF:

0.0129

Gnomad AMR exome

AF:

0.0235

Gnomad ASJ exome

AF:

0.0404

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.102

Gnomad NFE exome

AF:

0.0808

Gnomad OTH exome

AF:

0.0565

GnomAD4 exome

AF:

0.0728

AC:

106476

AN:

1461848

Hom.:

4480

Cov.:

AF XY:

0.0715

AC XY:

51978

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.0119

AC:

397

AN:

33480

American (AMR)

AF:

0.0248

AC:

1109

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0400

AC:

1046

AN:

26136

East Asian (EAS)

AF:

0.000126

AC:

AN:

39698

South Asian (SAS)

AF:

0.0239

AC:

2062

AN:

86258

European-Finnish (FIN)

AF:

0.0992

AC:

5299

AN:

53418

Middle Eastern (MID)

AF:

0.0286

AC:

165

AN:

5768

European-Non Finnish (NFE)

AF:

0.0833

AC:

92614

AN:

1111970

Other (OTH)

AF:

0.0626

AC:

3779

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

5744

11487

17231

22974

28718

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3394

6788

10182

13576

16970

<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:

0.0524

AC:

7974

AN:

152196

Hom.:

286

Cov.:

AF XY:

0.0524

AC XY:

3900

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0150

AC:

624

AN:

41544

American (AMR)

AF:

0.0284

AC:

434

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0418

AC:

145

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.0228

AC:

110

AN:

4814

European-Finnish (FIN)

AF:

0.103

AC:

1085

AN:

10576

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0796

AC:

5416

AN:

68014

Other (OTH)

AF:

0.0458

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

375

750

1124

1499

1874

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0699

Hom.:

1015

Bravo

AF:

0.0454

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0748

EpiControl

AF:

0.0695

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 12, 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

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cataract 33

Benign:1

Jan 28, 2025

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

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.051

(source)

DANN

Benign

0.64

PhyloP100

-2.6

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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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