20-17562692-C-T

Variant names:

• chr20-17562692-C-T
• rs6080737
• NM_001278608.2:c.-263+282G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001278608.2(BFSP1):​c.-263+282G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.901 in 152,152 control chromosomes in the GnomAD database, including 62,567 homozygotes. 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: 𝑓 0.90 (62567 hom., cov: 31)
• Consequence: BFSP1 NM_001278608.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278608.2. 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_001278608.2		c.-263+282G>A		intron	N/A	NP_001265537.1	Q12934-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BFSP1	ENST00000473415.1	TSL:3	n.172+282G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.901 AC: 136967 AN: 152034 Hom.: 62550 Cov.: 31

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.954

Gnomad AMR AF: 0.952

Gnomad ASJ AF: 0.960

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.963

Gnomad FIN AF: 0.946

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.970

Gnomad OTH AF: 0.916

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

GnomAD4 genome AF: 0.901 AC: 137027 AN: 152152 Hom.: 62567 Cov.: 31 AF XY: 0.904 AC XY: 67238 AN XY: 74398

African (AFR) AF: 0.729 AC: 30203 AN: 41452

American (AMR) AF: 0.952 AC: 14570 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.960 AC: 3333 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5168 AN: 5174

South Asian (SAS) AF: 0.963 AC: 4638 AN: 4816

European-Finnish (FIN) AF: 0.946 AC: 10038 AN: 10606

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.970 AC: 65987 AN: 68018

Other (OTH) AF: 0.917 AC: 1934 AN: 2110

Alfa AF: 0.861 Hom.: 18428

Bravo AF: 0.893

Asia WGS AF: 0.952 AC: 3313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.67
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6080737; hg19: chr20-17543337;