Genetic Variant BFSP2:p.Ala201Ala (chr3-133448519-G-A) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_003571.4(BFSP2):c.603G>A(p.Ala201Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 1,613,420 control chromosomes in the GnomAD database, including 282,437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 19696 hom., cov: 32)

Exomes 𝑓: 0.59 ( 262741 hom. )

Consequence

BFSP2
NM_003571.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.161

Publications

21 publications found

Variant links:

Genes affected

BFSP2 (HGNC:1041): (beaded filament structural protein 2) More than 99% of the vertebrate ocular lens is comprised of terminally differentiated lens fiber cells. Two lens-specific intermediate filament-like proteins, the protein product of this gene (phakinin), and filensin, are expressed only after fiber cell differentiation has begun. Both proteins are found in a structurally unique cytoskeletal element that is referred to as the beaded filament (BF). Mutations in this gene have been associated with juvenile-onset, progressive cataracts and Dowling-Meara epidermolysis bullosa simplex. [provided by RefSeq, Jun 2009]

BFSP2 links:

BFSP2-AS1 (HGNC:28425): (BFSP2 antisense RNA 1)

BFSP2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 3-133448519-G-A is Benign according to our data. Variant chr3-133448519-G-A is described in CliVar as Benign. Clinvar id is 1164247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-133448519-G-A is described in CliVar as Benign. Clinvar id is 1164247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.161 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BFSP2	NM_003571.4 link	c.603G>A	p.Ala201Ala	synonymous_variant	Exon 3 of 7	ENST00000302334.3	NP_003562.1	Q13515

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BFSP2	ENST00000302334.3 link	c.603G>A	p.Ala201Ala	synonymous_variant	Exon 3 of 7	1	NM_003571.4	ENSP00000304987.2		Q13515

Frequencies

GnomAD3 genomes

AF:

0.469

AC:

71279

AN:

151912

Hom.:

19695

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.791

Gnomad AMR

AF:

0.439

Gnomad ASJ

AF:

0.582

Gnomad EAS

AF:

0.583

Gnomad SAS

AF:

0.616

Gnomad FIN

AF:

0.539

Gnomad MID

AF:

0.598

Gnomad NFE

AF:

0.617

Gnomad OTH

AF:

0.500

GnomAD2 exomes

AF:

0.539

AC:

135182

AN:

251004

AF XY:

0.557

show subpopulations

Gnomad AFR exome

AF:

0.155

Gnomad AMR exome

AF:

0.349

Gnomad ASJ exome

AF:

0.554

Gnomad EAS exome

AF:

0.596

Gnomad FIN exome

AF:

0.539

Gnomad NFE exome

AF:

0.618

Gnomad OTH exome

AF:

0.561

GnomAD4 exome

AF:

0.593

AC:

866158

AN:

1461388

Hom.:

262741

Cov.:

AF XY:

0.596

AC XY:

433386

AN XY:

727040

show subpopulations

African (AFR)

AF:

0.149

AC:

4995

AN:

33476

American (AMR)

AF:

0.359

AC:

16050

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.560

AC:

14621

AN:

26130

East Asian (EAS)

AF:

0.559

AC:

22195

AN:

39692

South Asian (SAS)

AF:

0.618

AC:

53319

AN:

86236

European-Finnish (FIN)

AF:

0.547

AC:

29203

AN:

53404

Middle Eastern (MID)

AF:

0.565

AC:

3199

AN:

5660

European-Non Finnish (NFE)

AF:

0.619

AC:

688354

AN:

1111704

Other (OTH)

AF:

0.567

AC:

34222

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

19237

38473

57710

76946

96183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18248

36496

54744

72992

91240

<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:

0.469

AC:

71287

AN:

152032

Hom.:

19696

Cov.:

AF XY:

0.468

AC XY:

34779

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.168

AC:

6985

AN:

41470

American (AMR)

AF:

0.438

AC:

6692

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.582

AC:

2018

AN:

3470

East Asian (EAS)

AF:

0.583

AC:

3010

AN:

5166

South Asian (SAS)

AF:

0.618

AC:

2974

AN:

4814

European-Finnish (FIN)

AF:

0.539

AC:

5686

AN:

10546

Middle Eastern (MID)

AF:

0.622

AC:

183

AN:

294

European-Non Finnish (NFE)

AF:

0.617

AC:

41968

AN:

67982

Other (OTH)

AF:

0.500

AC:

1050

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1673

3346

5020

6693

8366

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

636

1272

1908

2544

3180

<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:

0.563

Hom.:

49064

Bravo

AF:

0.443

Asia WGS

AF:

0.553

AC:

1924

AN:

3478

EpiCase

AF:

0.615

EpiControl

AF:

0.618

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Cataract 12 multiple types

Benign:1

Feb 03, 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

-0.45

CADD

Benign

9.7

(source)

DANN

Benign

0.83

PhyloP100

0.16

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