rs34147780

Positions:

• chr20-17494579-GA-G
• chr20-17494579-GA-GAA

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_001195.5(BFSP1):​c.1492delT​(p.Ser498fs) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BFSP1 NM_001195.5 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.31

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.253 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BFSP1	NM_001195.5	c.1492delT	p.Ser498fs	frameshift_variant	8/8	ENST00000377873.8	NP_001186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BFSP1	ENST00000377873.8	c.1492delT	p.Ser498fs	frameshift_variant	8/8	1	NM_001195.5	ENSP00000367104.3
BFSP1	ENST00000377868.6	c.1117delT	p.Ser373fs	frameshift_variant	8/8	1		ENSP00000367099.2
BFSP1	ENST00000536626.7	c.1075delT	p.Ser359fs	frameshift_variant	9/9	2		ENSP00000442522.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs34147780; hg19: chr20-17475224;