20-17494075-TAA-T

Variant names:

• chr20-17494075-TAA-T
• rs548358901
• NM_001195.5:c.1995_1996delTT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 8P and 10B. PVS1 BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: 1.47
• Publications: 4 publications found

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

ACMG classification

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 VariationId 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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BFSP1	NM_001195.5	MANE Select	c.1995_1996delTT	p.Ter666LysfsTer8	frameshift stop_lost	Exon 8 of 8	NP_001186.1	Q12934-1
	BFSP1	NM_001424338.1		c.1887_1888delTT	p.Ter630LysfsTer8	frameshift stop_lost	Exon 7 of 7	NP_001411267.1
	BFSP1	NM_001278607.2		c.1662_1663delTT	p.Ter555LysfsTer8	frameshift stop_lost	Exon 8 of 8	NP_001265536.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BFSP1	ENST00000377873.8	TSL:1 MANE Select	c.1995_1996delTT	p.Ter666LysfsTer8	frameshift stop_lost	Exon 8 of 8	ENSP00000367104.3	Q12934-1
	BFSP1	ENST00000377868.6	TSL:1	c.1620_1621delTT	p.Ter541LysfsTer8	frameshift stop_lost	Exon 8 of 8	ENSP00000367099.2	Q12934-2
	BFSP1	ENST00000929672.1		c.1887_1888delTT	p.Ter630LysfsTer8	frameshift stop_lost	Exon 7 of 7	ENSP00000599731.1

Frequencies

GnomAD3 genomes AF: 0.00250 AC: 380 AN: 152236 Hom.: 0 Cov.: 33

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

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.: 13 AF XY: 0.00227 AC XY: 1646 AN XY: 724328

African (AFR) AF: 0.000151 AC: 5 AN: 33184

American (AMR) AF: 0.000542 AC: 24 AN: 44248

Ashkenazi Jewish (ASJ) AF: 0.000116 AC: 3 AN: 25916

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.0000701 AC: 6 AN: 85572

European-Finnish (FIN) AF: 0.0135 AC: 719 AN: 53296

Middle Eastern (MID) AF: 0.000348 AC: 2 AN: 5740

European-Non Finnish (NFE) AF: 0.00229 AC: 2540 AN: 1109074

Other (OTH) AF: 0.00198 AC: 119 AN: 60158

GnomAD4 genome AF: 0.00249 AC: 380 AN: 152354 Hom.: 0 Cov.: 33 AF XY: 0.00293 AC XY: 218 AN XY: 74506

African (AFR) AF: 0.000457 AC: 19 AN: 41588

American (AMR) AF: 0.00131 AC: 20 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0136 AC: 145 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00282 AC: 192 AN: 68032

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000516 Hom.: 1

Bravo AF: 0.00154

EpiCase AF: 0.00316

EpiControl AF: 0.00285

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Cataract 33 (1)
-	1	-	Congenital ocular coloboma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5
Mutation Taster		=195/5	polymorphism

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

Other links and lift over

dbSNP: rs548358901; hg19: chr20-17474720;