Genetic Variant BFSP2:c.489+9856C>T (chr3-133410428-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003571.4(BFSP2):c.489+9856C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 270,462 control chromosomes in the GnomAD database, including 21,588 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.35 ( 10895 hom., cov: 32)

Exomes 𝑓: 0.42 ( 10693 hom. )

Consequence

BFSP2
NM_003571.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.49

Publications

4 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:

AFF4P1 (HGNC:56526): (AFF4 pseudogene 1)

AFF4P1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BFSP2	NM_003571.4 link	c.489+9856C>T		intron_variant	Intron 1 of 6	ENST00000302334.3	NP_003562.1	Q13515
BFSP2	XM_017007315.2 link	c.489+9856C>T		intron_variant	Intron 1 of 5		XP_016862804.1	Q13515

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
BFSP2	ENST00000302334.3 link	c.489+9856C>T	intron_variant	Intron 1 of 6	1	NM_003571.4	ENSP00000304987.2	Q13515
AFF4P1	ENST00000510575.1 link	n.474C>T	non_coding_transcript_exon_variant	Exon 1 of 1	6
BFSP2	ENST00000511140.1 link	n.112-1860C>T	intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.354

AC:

53709

AN:

151876

Hom.:

10894

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.213

Gnomad AMR

AF:

0.413

Gnomad ASJ

AF:

0.490

Gnomad EAS

AF:

0.502

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.490

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.423

Gnomad OTH

AF:

0.386

GnomAD4 exome

AF:

0.421

AC:

49901

AN:

118468

Hom.:

10693

Cov.:

AF XY:

0.419

AC XY:

28670

AN XY:

68346

show subpopulations

African (AFR)

AF:

0.127

AC:

319

AN:

2520

American (AMR)

AF:

0.461

AC:

3765

AN:

8164

Ashkenazi Jewish (ASJ)

AF:

0.464

AC:

948

AN:

2044

East Asian (EAS)

AF:

0.465

AC:

1983

AN:

4264

South Asian (SAS)

AF:

0.397

AC:

7052

AN:

17766

European-Finnish (FIN)

AF:

0.481

AC:

4214

AN:

8764

Middle Eastern (MID)

AF:

0.434

AC:

338

AN:

778

European-Non Finnish (NFE)

AF:

0.421

AC:

28763

AN:

68392

Other (OTH)

AF:

0.436

AC:

2519

AN:

5776

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1278

2556

3834

5112

6390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

222

444

666

888

1110

<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:

0.354

AC:

53736

AN:

151994

Hom.:

10895

Cov.:

AF XY:

0.359

AC XY:

26706

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.146

AC:

6058

AN:

41476

American (AMR)

AF:

0.413

AC:

6311

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.490

AC:

1699

AN:

3470

East Asian (EAS)

AF:

0.502

AC:

2597

AN:

5172

South Asian (SAS)

AF:

0.427

AC:

2058

AN:

4816

European-Finnish (FIN)

AF:

0.490

AC:

5161

AN:

10542

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.423

AC:

28724

AN:

67926

Other (OTH)

AF:

0.386

AC:

815

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1672

3343

5015

6686

8358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<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:

0.392

Hom.:

5057

Bravo

AF:

0.337

Asia WGS

AF:

0.430

AC:

1496

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.61

PhyloP100

2.5

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

Computational scores

Splicing

Publications

Other links and lift over