20-17498813-C-G

Variant names:

• chr20-17498813-C-G
• rs202146533
• NM_001195.5:c.956+7G>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001195.5(BFSP1):​c.956+7G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,611,390 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00081 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (5 hom.)
• Consequence: BFSP1 NM_001195.5 splice_region, intron
• Scores: Splicing: ADA: 0.003561
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.539

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 20-17498813-C-G is Benign according to our data. Variant chr20-17498813-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 474092.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-17498813-C-G is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000814 (124/152308) while in subpopulation NFE AF= 0.00151 (103/68018). AF 95% confidence interval is 0.00128. There are 0 homozygotes in gnomad4. There are 46 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 5 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BFSP1	NM_001195.5	c.956+7G>C		splice_region_variant, intron_variant	Intron 6 of 7	ENST00000377873.8	NP_001186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BFSP1	ENST00000377873.8	c.956+7G>C		splice_region_variant, intron_variant	Intron 6 of 7	1	NM_001195.5	ENSP00000367104.3
BFSP1	ENST00000377868.6	c.581+7G>C		splice_region_variant, intron_variant	Intron 6 of 7	1		ENSP00000367099.2
BFSP1	ENST00000536626.7	c.539+7G>C		splice_region_variant, intron_variant	Intron 7 of 8	2		ENSP00000442522.1

Frequencies

GnomAD3 genomes AF: 0.000815 AC: 124 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00151

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.000632 AC: 157 AN: 248318 Hom.: 0 AF XY: 0.000618 AC XY: 83 AN XY: 134370

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.000786

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000470

Gnomad NFE exome AF: 0.00109

Gnomad OTH exome AF: 0.000825

GnomAD4 exome AF: 0.00151 AC: 2200 AN: 1459082 Hom.: 5 Cov.: 31 AF XY: 0.00145 AC XY: 1054 AN XY: 725750

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.00103

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000113

Gnomad4 NFE exome AF: 0.00185

Gnomad4 OTH exome AF: 0.00130

GnomAD4 genome AF: 0.000814 AC: 124 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.000618 AC XY: 46 AN XY: 74462

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00151

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.000299 Hom.: 0

Bravo AF: 0.000876

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Cataract 33 Benign:1

Dec 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

BFSP1-related disorder Benign:1

May 06, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.4
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0036
dbscSNV1_RF	Benign	0.030
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: rs202146533; hg19: chr20-17479458;