20-17509088-G-T

Variant names:

• chr20-17509088-G-T
• rs2281207
• NM_001195.5:c.628-92C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001195.5(BFSP1):​c.628-92C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000267 in 750,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: BFSP1 NM_001195.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• Publications: 5 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

ENSG00000294980 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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.628-92C>A		intron	N/A	NP_001186.1	Q12934-1
	BFSP1	NM_001424338.1		c.627+2888C>A		intron	N/A	NP_001411267.1
	BFSP1	NM_001278607.2		c.295-92C>A		intron	N/A	NP_001265536.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BFSP1	ENST00000377873.8	TSL:1 MANE Select	c.628-92C>A		intron	N/A	ENSP00000367104.3	Q12934-1
	BFSP1	ENST00000377868.6	TSL:1	c.253-92C>A		intron	N/A	ENSP00000367099.2	Q12934-2
	BFSP1	ENST00000929672.1		c.627+2888C>A		intron	N/A	ENSP00000599731.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000267 AC: 2 AN: 750048 Hom.: 0 AF XY: 0.00000267 AC XY: 1 AN XY: 374750

African (AFR) AF: 0.0000606 AC: 1 AN: 16512

American (AMR) AF: 0.00 AC: 0 AN: 13246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14638

East Asian (EAS) AF: 0.00 AC: 0 AN: 27318

South Asian (SAS) AF: 0.00 AC: 0 AN: 42260

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29926

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4160

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 566996

Other (OTH) AF: 0.0000286 AC: 1 AN: 34992

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 88

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.012
DANN	Benign	0.66
PhyloP100		-2.1

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: rs2281207; hg19: chr20-17489733;