NM_003571.4:c.1220C>A

Variant names:

Variant summary

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

The NM_003571.4(BFSP2):c.1220C>A(p.Ala407Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0435 in 1,612,172 control chromosomes in the GnomAD database, including 1,686 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 137 hom., cov: 33)

Exomes 𝑓: 0.044 ( 1549 hom. )

Consequence

BFSP2
NM_003571.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.09

Publications

9 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007096857).

BP6

Variant 3-133472541-C-A is Benign according to our data. Variant chr3-133472541-C-A is described in ClinVar as Benign. ClinVar VariationId is 259089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003571.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BFSP2	NM_003571.4	MANE Select	c.1220C>A	p.Ala407Asp	missense	Exon 6 of 7	NP_003562.1	Q13515
BFSP2-AS1	NR_135276.2		n.209-17078G>T		intron	N/A
BFSP2-AS1	NR_135277.2		n.209-17078G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BFSP2	ENST00000302334.3	TSL:1 MANE Select	c.1220C>A	p.Ala407Asp	missense	Exon 6 of 7	ENSP00000304987.2	Q13515
BFSP2	ENST00000503047.1	TSL:2	n.200C>A		non_coding_transcript_exon	Exon 1 of 2
BFSP2	ENST00000510039.1	TSL:3	n.365C>A		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes

AF:

0.0413

AC:

6287

AN:

152212

Hom.:

134

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0357

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0355

Gnomad ASJ

AF:

0.0691

Gnomad EAS

AF:

0.0233

Gnomad SAS

AF:

0.0586

Gnomad FIN

AF:

0.0461

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0437

Gnomad OTH

AF:

0.0622

GnomAD2 exomes

AF:

0.0447

AC:

10991

AN:

245866

AF XY:

0.0471

show subpopulations

Gnomad AFR exome

AF:

0.0353

Gnomad AMR exome

AF:

0.0269

Gnomad ASJ exome

AF:

0.0713

Gnomad EAS exome

AF:

0.0277

Gnomad FIN exome

AF:

0.0451

Gnomad NFE exome

AF:

0.0464

Gnomad OTH exome

AF:

0.0455

GnomAD4 exome

AF:

0.0438

AC:

63893

AN:

1459842

Hom.:

1549

Cov.:

AF XY:

0.0446

AC XY:

32420

AN XY:

726220

show subpopulations

African (AFR)

AF:

0.0361

AC:

1206

AN:

33420

American (AMR)

AF:

0.0275

AC:

1227

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.0686

AC:

1790

AN:

26104

East Asian (EAS)

AF:

0.0182

AC:

724

AN:

39692

South Asian (SAS)

AF:

0.0639

AC:

5506

AN:

86130

European-Finnish (FIN)

AF:

0.0450

AC:

2400

AN:

53366

Middle Eastern (MID)

AF:

0.0734

AC:

324

AN:

4414

European-Non Finnish (NFE)

AF:

0.0431

AC:

47949

AN:

1111846

Other (OTH)

AF:

0.0460

AC:

2767

AN:

60204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

3955

7911

11866

15822

19777

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1800

3600

5400

7200

9000

<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:

0.0414

AC:

6299

AN:

152330

Hom.:

137

Cov.:

AF XY:

0.0411

AC XY:

3064

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0358

AC:

1490

AN:

41586

American (AMR)

AF:

0.0355

AC:

543

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0691

AC:

240

AN:

3472

East Asian (EAS)

AF:

0.0234

AC:

121

AN:

5182

South Asian (SAS)

AF:

0.0582

AC:

281

AN:

4826

European-Finnish (FIN)

AF:

0.0461

AC:

490

AN:

10618

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0437

AC:

2975

AN:

68024

Other (OTH)

AF:

0.0634

AC:

134

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

316

632

949

1265

1581

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<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:

0.0450

Hom.:

550

Bravo

AF:

0.0411

TwinsUK

AF:

0.0423

AC:

157

ALSPAC

AF:

0.0381

AC:

147

ESP6500AA

AF:

0.0325

AC:

143

ESP6500EA

AF:

0.0441

AC:

379

ExAC

AF:

0.0443

AC:

5372

Asia WGS

AF:

0.0470

AC:

164

AN:

3478

EpiCase

AF:

0.0481

EpiControl

AF:

0.0485

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cataract 12 multiple types (2)

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

Eigen

Benign

0.15

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0071

MetaSVM

Benign

-0.48

MutationAssessor

Benign

1.4

PhyloP100

3.1

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.31

Sift

Benign

0.59

Sift4G

Uncertain

0.047

Polyphen

0.92

Vest4

0.16

MPC

0.67

ClinPred

0.019

GERP RS

2.3

Varity_R

0.45

gMVP

0.43

Mutation Taster

=81/19

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over