Variant rs548358901 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 8P and 10B. PVS1BP6_ModerateBS1BS2

The NM_001195.5(BFSP1):c.1995_1996del(p.Ter666LysfsTer8) variant causes a frameshift, stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00236 in 1,609,184 control chromosomes in the GnomAD database, including 13 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 13 hom. )

Consequence

BFSP1
NM_001195.5 frameshift, stop_lost

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 1.47

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PVS1

Stoplost variant. No alternative stopcodon identified downstream, so we assume a Nonstop Mediated Decay. LoF is a known mechanism of disease.

BP6

Variant 20-17494075-TAA-T is Benign according to our data. Variant chr20-17494075-TAA-T is described in ClinVar as [Benign]. Clinvar id is 68470.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-17494075-TAA-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00249 (380/152354) while in subpopulation NFE AF= 0.00282 (192/68032). AF 95% confidence interval is 0.0025. There are 0 homozygotes in gnomad4. There are 218 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 13 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BFSP1	NM_001195.5 linkuse as main transcript	c.1995_1996del	p.Ter666LysfsTer8	frameshift_variant, stop_lost	8/8	ENST00000377873.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BFSP1	ENST00000377873.8 linkuse as main transcript	c.1995_1996del	p.Ter666LysfsTer8	frameshift_variant, stop_lost	8/8	1	NM_001195.5	P1	Q12934-1
BFSP1	ENST00000377868.6 linkuse as main transcript	c.1620_1621del	p.Ter541LysfsTer8	frameshift_variant, stop_lost	8/8	1			Q12934-2
BFSP1	ENST00000536626.7 linkuse as main transcript	c.1578_1579del	p.Ter527LysfsTer8	frameshift_variant, stop_lost	9/9	2			Q12934-3

Frequencies

GnomAD3 genomes

AF:

0.00250

AC:

380

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0136

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00282

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00275

AC:

684

AN:

248512

Hom.:

AF XY:

0.00270

AC XY:

363

AN XY:

134326

show subpopulations

Gnomad AFR exome

AF:

0.000248

Gnomad AMR exome

AF:

0.000644

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000134

Gnomad FIN exome

AF:

0.0128

Gnomad NFE exome

AF:

0.00321

Gnomad OTH exome

AF:

0.00282

GnomAD4 exome

AF:

0.00235

AC:

3418

AN:

1456830

Hom.:

AF XY:

0.00227

AC XY:

1646

AN XY:

724328

show subpopulations

Gnomad4 AFR exome

AF:

0.000151

Gnomad4 AMR exome

AF:

0.000542

Gnomad4 ASJ exome

AF:

0.000116

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000701

Gnomad4 FIN exome

AF:

0.0135

Gnomad4 NFE exome

AF:

0.00229

Gnomad4 OTH exome

AF:

0.00198

GnomAD4 genome

AF:

0.00249

AC:

380

AN:

152354

Hom.:

Cov.:

AF XY:

0.00293

AC XY:

218

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0136

Gnomad4 NFE

AF:

0.00282

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000516

Hom.:

Bravo

AF:

0.00154

EpiCase

AF:

0.00316

EpiControl

AF:

0.00285

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital ocular coloboma

Uncertain:1

Uncertain significance, no assertion criteria provided

research

Eye Genetics Research Group, Children's Medical Research Institute

Mar 30, 2012

- -

Cataract 33

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 09, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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