NM_001195.5:c.1995_1996delTT

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 8P and 10B. PVS1BP6_ModerateBS1BS2

The NM_001195.5(BFSP1):c.1995_1996delTT(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

Publications

4 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 -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.

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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 13 AR,AD,SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BFSP1	NM_001195.5 link	c.1995_1996delTT	p.Ter666LysfsTer8	frameshift_variant, stop_lost	Exon 8 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.1995_1996delTT	p.Ter666LysfsTer8	frameshift_variant, stop_lost	Exon 8 of 8	1	NM_001195.5	ENSP00000367104.3	Q12934-1
BFSP1	ENST00000377868.6 link	c.1620_1621delTT	p.Ter541LysfsTer8	frameshift_variant, stop_lost	Exon 8 of 8	1		ENSP00000367099.2	Q12934-2
BFSP1	ENST00000536626.7 link	c.1578_1579delTT	p.Ter527LysfsTer8	frameshift_variant, stop_lost	Exon 9 of 9	2		ENSP00000442522.1	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

GnomAD2 exomes

AF:

0.00275

AC:

684

AN:

248512

AF XY:

0.00270

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 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

African (AFR)

AF:

0.000151

AC:

AN:

33184

American (AMR)

AF:

0.000542

AC:

AN:

44248

Ashkenazi Jewish (ASJ)

AF:

0.000116

AC:

AN:

25916

East Asian (EAS)

AF:

0.00

AC:

AN:

39642

South Asian (SAS)

AF:

0.0000701

AC:

AN:

85572

European-Finnish (FIN)

AF:

0.0135

AC:

719

AN:

53296

Middle Eastern (MID)

AF:

0.000348

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00229

AC:

2540

AN:

1109074

Other (OTH)

AF:

0.00198

AC:

119

AN:

60158

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

183

367

550

734

917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00249

AC:

380

AN:

152354

Hom.:

Cov.:

AF XY:

0.00293

AC XY:

218

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.000457

AC:

AN:

41588

American (AMR)

AF:

0.00131

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0136

AC:

145

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00282

AC:

192

AN:

68032

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Mar 30, 2012

Eye Genetics Research Group, Children's Medical Research Institute

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:research

- -

Cataract 33

Benign:1

Nov 05, 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

PhyloP100

1.5

Mutation Taster

=195/5

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

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

NM_001195.5:c.1995_1996delTT

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