dbSNP rs1153876: BFSP2:c.489+4320G>A (chr3-133404892-G-A) – 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+4320G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,022 control chromosomes in the GnomAD database, including 20,074 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 0.51 ( 20071 hom., cov: 32)

Exomes 𝑓: 0.69 ( 3 hom. )

Consequence

BFSP2
NM_003571.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.925

Publications

2 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 Gene-Disease associations (from GenCC):

cataract 12 multiple types
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
early-onset non-syndromic cataract
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
early-onset lamellar cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
early-onset sutural cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
pulverulent cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

BFSP2 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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BFSP2	NM_003571.4 link	c.489+4320G>A		intron_variant	Intron 1 of 6	ENST00000302334.3	NP_003562.1	Q13515
BFSP2	XM_017007315.2 link	c.489+4320G>A		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+4320G>A	intron_variant	Intron 1 of 6	1	NM_003571.4	ENSP00000304987.2	Q13515
BFSP2	ENST00000511140.1 link	n.111+4320G>A	intron_variant	Intron 1 of 1	3
BFSP2	ENST00000513441.1 link	n.*18G>A	downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.513

AC:

77868

AN:

151888

Hom.:

20052

Cov.:

show subpopulations

Gnomad AFR

AF:

0.452

Gnomad AMI

AF:

0.402

Gnomad AMR

AF:

0.504

Gnomad ASJ

AF:

0.563

Gnomad EAS

AF:

0.546

Gnomad SAS

AF:

0.534

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.509

Gnomad NFE

AF:

0.537

Gnomad OTH

AF:

0.522

GnomAD4 exome

AF:

0.688

AC:

AN:

Hom.:

Cov.:

AF XY:

0.667

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.700

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.513

AC:

77926

AN:

152006

Hom.:

20071

Cov.:

AF XY:

0.514

AC XY:

38209

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.452

AC:

18722

AN:

41450

American (AMR)

AF:

0.504

AC:

7703

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.563

AC:

1954

AN:

3468

East Asian (EAS)

AF:

0.545

AC:

2815

AN:

5162

South Asian (SAS)

AF:

0.534

AC:

2568

AN:

4810

European-Finnish (FIN)

AF:

0.570

AC:

6021

AN:

10556

Middle Eastern (MID)

AF:

0.520

AC:

153

AN:

294

European-Non Finnish (NFE)

AF:

0.537

AC:

36517

AN:

67972

Other (OTH)

AF:

0.524

AC:

1106

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1975

3950

5925

7900

9875

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

716

1432

2148

2864

3580

<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:

0.428

Hom.:

1540

Bravo

AF:

0.502

Asia WGS

AF:

0.519

AC:

1809

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

9.3

(source)

DANN

Benign

0.83

PhyloP100

0.93

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