Genetic Variant BFSP1:c.*132C>T (chr20-17493942-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001195.5(BFSP1):c.*132C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0233 in 821,954 control chromosomes in the GnomAD database, including 444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 89 hom., cov: 32)

Exomes 𝑓: 0.024 ( 355 hom. )

Consequence

BFSP1
NM_001195.5 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.201

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 20-17493942-G-A is Benign according to our data. Variant chr20-17493942-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1213460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BFSP1	NM_001195.5 link	c.*132C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000377873.8	NP_001186.1	Q12934-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
BFSP1	ENST00000377873 link	c.*132C>T	3_prime_UTR_variant	Exon 8 of 8	1	NM_001195.5	ENSP00000367104.3	Q12934-1
BFSP1	ENST00000377868 link	c.*132C>T	3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000367099.2	Q12934-2
BFSP1	ENST00000536626 link	c.*132C>T	3_prime_UTR_variant	Exon 9 of 9	2		ENSP00000442522.1	Q12934-3

Frequencies

GnomAD3 genomes

AF:

0.0210

AC:

3199

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00466

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0575

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.0276

Gnomad FIN

AF:

0.0207

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0174

Gnomad OTH

AF:

0.0153

GnomAD4 exome

AF:

0.0238

AC:

15957

AN:

669686

Hom.:

355

Cov.:

AF XY:

0.0237

AC XY:

8097

AN XY:

341948

show subpopulations

Gnomad4 AFR exome

AF:

0.00345

AC:

AN:

16798

Gnomad4 AMR exome

AF:

0.0546

AC:

1143

AN:

20926

Gnomad4 ASJ exome

AF:

0.000397

AC:

AN:

15132

Gnomad4 EAS exome

AF:

0.0990

AC:

3334

AN:

33692

Gnomad4 SAS exome

AF:

0.0265

AC:

1234

AN:

46544

Gnomad4 FIN exome

AF:

0.0214

AC:

824

AN:

38522

Gnomad4 NFE exome

AF:

0.0187

AC:

8637

AN:

460776

Gnomad4 Remaining exome

AF:

0.0214

AC:

713

AN:

33312

Heterozygous variant carriers

733

1466

2200

2933

3666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

262

524

786

1048

1310

<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:

0.0210

AC:

3195

AN:

152268

Hom.:

Cov.:

AF XY:

0.0223

AC XY:

1660

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00464

AC:

0.00464389

AN:

0.00464389

Gnomad4 AMR

AF:

0.0574

AC:

0.0574006

AN:

0.0574006

Gnomad4 ASJ

AF:

0.000576

AC:

0.000576037

AN:

0.000576037

Gnomad4 EAS

AF:

0.107

AC:

0.106618

AN:

0.106618

Gnomad4 SAS

AF:

0.0274

AC:

0.0274086

AN:

0.0274086

Gnomad4 FIN

AF:

0.0207

AC:

0.0207312

AN:

0.0207312

Gnomad4 NFE

AF:

0.0174

AC:

0.0174497

AN:

0.0174497

Gnomad4 OTH

AF:

0.0151

AC:

0.0151229

AN:

0.0151229

Heterozygous variant carriers

152

305

457

610

762

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0206

Hom.:

Bravo

AF:

0.0226

Asia WGS

AF:

0.0530

AC:

183

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 21, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.3

DANN

Benign

0.59

Mutation Taster

=100/0

polymorphism (auto)

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over