20-17559507-G-A

Variant names:

• chr20-17559507-G-A
• rs763394
• NM_001278608.2:c.-41+850C>T

Variant summary

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

The NM_001278608.2(BFSP1):​c.-41+850C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0475 in 152,194 control chromosomes in the GnomAD database, including 251 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 0.047 (251 hom., cov: 32)
• Consequence: BFSP1 NM_001278608.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0918 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BFSP1	NM_001278608.2		c.-41+850C>T		intron	N/A	NP_001265537.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BFSP1	ENST00000473415.1	TSL:3	n.471+850C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0474 AC: 7206 AN: 152076 Hom.: 249 Cov.: 32

Gnomad AFR AF: 0.0941

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.0213

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0365

Gnomad FIN AF: 0.0532

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0291

Gnomad OTH AF: 0.0407

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

GnomAD4 genome AF: 0.0475 AC: 7225 AN: 152194 Hom.: 251 Cov.: 32 AF XY: 0.0469 AC XY: 3490 AN XY: 74398

African (AFR) AF: 0.0943 AC: 3913 AN: 41508

American (AMR) AF: 0.0213 AC: 326 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0372 AC: 129 AN: 3472

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5172

South Asian (SAS) AF: 0.0367 AC: 177 AN: 4824

European-Finnish (FIN) AF: 0.0532 AC: 564 AN: 10600

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0291 AC: 1978 AN: 68010

Other (OTH) AF: 0.0403 AC: 85 AN: 2110

Alfa AF: 0.0411 Hom.: 172

Bravo AF: 0.0467

Asia WGS AF: 0.0360 AC: 125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.71
PhyloP100		0.19
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: rs763394; hg19: chr20-17540152;