rs2281207

Positions:

• chr20-17509088-G-A
• chr20-17509088-G-C
• chr20-17509088-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001195.5(BFSP1):​c.628-92C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 901,020 control chromosomes in the GnomAD database, including 14,527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2789 hom., cov: 33)
  • Exomes 𝑓: 0.16 (11738 hom.)
• Consequence: BFSP1 NM_001195.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.08

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 20-17509088-G-A is Benign according to our data. Variant chr20-17509088-G-A is described in ClinVar as [Benign]. Clinvar id is 1287293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BFSP1	NM_001195.5	c.628-92C>T		intron_variant		ENST00000377873.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BFSP1	ENST00000377873.8	c.628-92C>T		intron_variant		1	NM_001195.5	P1
BFSP1	ENST00000377868.6	c.253-92C>T		intron_variant		1
BFSP1	ENST00000536626.7	c.211-92C>T		intron_variant		2
BFSP1	ENST00000492424.1	n.115-92C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26884 AN: 152026 Hom.: 2779 Cov.: 33

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.0957

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.159 AC: 119153 AN: 748878 Hom.: 11738 AF XY: 0.164 AC XY: 61207 AN XY: 374182

Gnomad4 AFR exome AF: 0.221

Gnomad4 AMR exome AF: 0.212

Gnomad4 ASJ exome AF: 0.158

Gnomad4 EAS exome AF: 0.425

Gnomad4 SAS exome AF: 0.311

Gnomad4 FIN exome AF: 0.109

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.178

GnomAD4 genome AF: 0.177 AC: 26923 AN: 152142 Hom.: 2789 Cov.: 33 AF XY: 0.181 AC XY: 13474 AN XY: 74384

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.0957

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.187

Alfa AF: 0.0597 Hom.: 74

Bravo AF: 0.184

Asia WGS AF: 0.401 AC: 1393 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.037
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs2281207; hg19: chr20-17489733;