rs886038419

Positions:

• chr20-17531223-GC-AA

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_001195.5(BFSP1):​c.106_107delGCinsTT​(p.Ala36Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BFSP1 NM_001195.5 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: 0.793

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 20-17531223-GC-AA is Benign according to our data. Variant chr20-17531223-GC-AA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 257613.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=2}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BFSP1	NM_001195.5	c.106_107delGCinsTT	p.Ala36Phe	missense_variant		ENST00000377873.8	NP_001186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BFSP1	ENST00000377873.8	c.106_107delGCinsTT	p.Ala36Phe	missense_variant		1	NM_001195.5	ENSP00000367104.3
BFSP1	ENST00000377868.6	c.3-6316_3-6315delGCinsTT		intron_variant		1		ENSP00000367099.2
BFSP1	ENST00000536626.7	c.-40-6316_-40-6315delGCinsTT		intron_variant		2		ENSP00000442522.1
BFSP1	ENST00000473415.1	n.472-6316_472-6315delGCinsTT		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Feb 05, 2021

In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Cataract 33 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 14, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs886038419; hg19: chr20-17511868; COSMIC: COSV105309564;