rs16999416

chr20-17561185-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BFSP1	NM_001278608.2	c.-262-607C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BFSP1	ENST00000473415.1	n.173-402C>T		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.0814

Gnomad4 ASJ AF: 0.0657

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.0317

Gnomad4 FIN AF: 0.0815

Gnomad4 NFE AF: 0.0953

Gnomad4 OTH AF: 0.112

Alfa AF: 0.100 Hom.: 180

Bravo AF: 0.103

Asia WGS AF: 0.0450 AC: 155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.2
Dann	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16999416; hg19: chr20-17541830;