NM_001195.5:c.137G>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001195.5(BFSP1):c.137G>C(p.Gly46Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,304,188 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G46W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0091 ( 25 hom., cov: 33)

Exomes 𝑓: 0.00073 ( 12 hom. )

Consequence

BFSP1
NM_001195.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.83

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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009263337).

BP6

Variant 20-17531193-C-G is Benign according to our data. Variant chr20-17531193-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 474089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00911 (1381/151604) while in subpopulation AFR AF = 0.0308 (1276/41460). AF 95% confidence interval is 0.0294. There are 25 homozygotes in GnomAd4. There are 624 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 25 AR,AD,SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BFSP1	NM_001195.5 link	c.137G>C	p.Gly46Ala	missense_variant	Exon 1 of 8	ENST00000377873.8	NP_001186.1	Q12934-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BFSP1	ENST00000377873.8 link	c.137G>C	p.Gly46Ala	missense_variant	Exon 1 of 8	1	NM_001195.5	ENSP00000367104.3	Q12934-1
BFSP1	ENST00000377868.6 link	c.3-6285G>C		intron_variant	Intron 1 of 7	1		ENSP00000367099.2	Q12934-2
BFSP1	ENST00000536626.7 link	c.-40-6285G>C		intron_variant	Intron 2 of 8	2		ENSP00000442522.1	Q12934-3
BFSP1	ENST00000473415.1 link	n.472-6285G>C		intron_variant	Intron 4 of 6	3

Frequencies

GnomAD3 genomes

AF:

0.00912

AC:

1381

AN:

151496

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0309

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00553

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:

0.0000442

Gnomad OTH

AF:

0.00864

GnomAD2 exomes

AF:

0.000662

AC:

AN:

13596

AF XY:

0.000604

show subpopulations

Gnomad AFR exome

AF:

0.0214

Gnomad AMR exome

AF:

0.000854

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00224

GnomAD4 exome

AF:

0.000729

AC:

840

AN:

1152584

Hom.:

Cov.:

AF XY:

0.000642

AC XY:

358

AN XY:

557980

show subpopulations

African (AFR)

AF:

0.0320

AC:

739

AN:

23126

American (AMR)

AF:

0.00175

AC:

AN:

10888

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15502

East Asian (EAS)

AF:

0.00

AC:

AN:

25646

South Asian (SAS)

AF:

0.0000239

AC:

AN:

41878

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26130

Middle Eastern (MID)

AF:

0.000633

AC:

AN:

3162

European-Non Finnish (NFE)

AF:

0.0000167

AC:

AN:

960184

Other (OTH)

AF:

0.00137

AC:

AN:

46068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

144

192

240

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.00911

AC:

1381

AN:

151604

Hom.:

Cov.:

AF XY:

0.00842

AC XY:

624

AN XY:

74122

show subpopulations

African (AFR)

AF:

0.0308

AC:

1276

AN:

41460

American (AMR)

AF:

0.00553

AC:

AN:

15200

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000442

AC:

AN:

67824

Other (OTH)

AF:

0.00855

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

136

205

273

341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00680

Hom.:

Bravo

AF:

0.0104

ExAC

AF:

0.0000984

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 16, 2024

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Cataract 33

Benign:1

Nov 26, 2024

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

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.40

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0093

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.69

PhyloP100

2.8

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.96

REVEL

Benign

0.19

Sift

Benign

0.86

Sift4G

Benign

0.82

Polyphen

0.034

Vest4

0.15

MVP

0.73

MPC

1.3

ClinPred

0.016

GERP RS

1.6

PromoterAI

0.045

Neutral

(source)

Varity_R

0.040

gMVP

0.25

Mutation Taster

=95/5

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

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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