20-17494393-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_001195.5(BFSP1):c.1679G>A(p.Arg560His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000138 in 1,614,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R560C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

BFSP1
NM_001195.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: -0.662

Publications

1 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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.037938565).

BS1

Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.000144 (211/1461892) while in subpopulation NFE AF = 0.000182 (202/1112010). AF 95% confidence interval is 0.000161. There are 0 homozygotes in GnomAdExome4. There are 101 alleles in the male GnomAdExome4 subpopulation. Median coverage is 57. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BFSP1	NM_001195.5	MANE Select	c.1679G>A	p.Arg560His	missense	Exon 8 of 8	NP_001186.1	Q12934-1
BFSP1	NM_001424338.1		c.1571G>A	p.Arg524His	missense	Exon 7 of 7	NP_001411267.1
BFSP1	NM_001278607.2		c.1346G>A	p.Arg449His	missense	Exon 8 of 8	NP_001265536.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BFSP1	ENST00000377873.8	TSL:1 MANE Select	c.1679G>A	p.Arg560His	missense	Exon 8 of 8	ENSP00000367104.3	Q12934-1
BFSP1	ENST00000377868.6	TSL:1	c.1304G>A	p.Arg435His	missense	Exon 8 of 8	ENSP00000367099.2	Q12934-2
BFSP1	ENST00000929672.1		c.1571G>A	p.Arg524His	missense	Exon 7 of 7	ENSP00000599731.1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000318

AC:

AN:

251478

AF XY:

0.0000368

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000144

AC:

211

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

101

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000182

AC:

202

AN:

1112010

Other (OTH)

AF:

0.0000993

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

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:

0.0000723

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41454

American (AMR)

AF:

0.000131

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cataract 33 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.24

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.039

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.43

M_CAP

Benign

0.0069

MetaRNN

Benign

0.038

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.41

PhyloP100

-0.66

PrimateAI

Benign

0.17

PROVEAN

Benign

-0.31

REVEL

Benign

0.0090

Sift

Benign

0.21

Sift4G

Benign

0.18

Polyphen

0.0010

Vest4

0.054

MVP

0.11

MPC

0.090

ClinPred

0.028

GERP RS

-7.8

Varity_R

0.015

gMVP

0.053

Mutation Taster

=94/6

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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