rs16999416

Variant names:

• chr20-17561185-G-A
• rs16999416
• NM_001278608.2:c.-262-607C>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.-262-607C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,190 control chromosomes in the GnomAD database, including 883 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 0.10 (883 hom., cov: 33)
• Consequence: BFSP1 NM_001278608.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.676
• 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 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.-262-607C>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.173-402C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15279 AN: 152072 Hom.: 881 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0816

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.0325

Gnomad FIN AF: 0.0815

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0953

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.100 AC: 15294 AN: 152190 Hom.: 883 Cov.: 33 AF XY: 0.0978 AC XY: 7278 AN XY: 74406

African (AFR) AF: 0.144 AC: 5981 AN: 41510

American (AMR) AF: 0.0814 AC: 1244 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0657 AC: 228 AN: 3470

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5184

South Asian (SAS) AF: 0.0317 AC: 153 AN: 4824

European-Finnish (FIN) AF: 0.0815 AC: 864 AN: 10598

Middle Eastern (MID) AF: 0.0616 AC: 18 AN: 292

European-Non Finnish (NFE) AF: 0.0953 AC: 6479 AN: 68008

Other (OTH) AF: 0.112 AC: 235 AN: 2106

Alfa AF: 0.101 Hom.: 188

Bravo AF: 0.103

Asia WGS AF: 0.0450 AC: 155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.66
PhyloP100		-0.68
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: rs16999416; hg19: chr20-17541830;