20-17494323-T-C

Position:

• chr20-17494323-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001195.5(BFSP1):​c.1749A>G​(p.Pro583=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 1,614,018 control chromosomes in the GnomAD database, including 418,907 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P583P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.74 (41399 hom., cov: 33)
  • Exomes 𝑓: 0.72 (377508 hom.)
• Consequence: BFSP1 NM_001195.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -5.31

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 20-17494323-T-C is Benign according to our data. Variant chr20-17494323-T-C is described in ClinVar as [Benign]. Clinvar id is 257615.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-17494323-T-C is described in Lovd as [Benign]. Variant chr20-17494323-T-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-5.31 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BFSP1	NM_001195.5	c.1749A>G	p.Pro583=	synonymous_variant	8/8	ENST00000377873.8	NP_001186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BFSP1	ENST00000377873.8	c.1749A>G	p.Pro583=	synonymous_variant	8/8	1	NM_001195.5	ENSP00000367104	P1
BFSP1	ENST00000377868.6	c.1374A>G	p.Pro458=	synonymous_variant	8/8	1		ENSP00000367099
BFSP1	ENST00000536626.7	c.1332A>G	p.Pro444=	synonymous_variant	9/9	2		ENSP00000442522

Frequencies

GnomAD3 genomes AF: 0.736 AC: 111949 AN: 152026 Hom.: 41366 Cov.: 33

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.710

Gnomad OTH AF: 0.743

GnomAD3 exomes AF: 0.731 AC: 183735 AN: 251436 Hom.: 67519 AF XY: 0.730 AC XY: 99237 AN XY: 135898

Gnomad AFR exome AF: 0.790

Gnomad AMR exome AF: 0.810

Gnomad ASJ exome AF: 0.762

Gnomad EAS exome AF: 0.648

Gnomad SAS exome AF: 0.787

Gnomad FIN exome AF: 0.658

Gnomad NFE exome AF: 0.708

Gnomad OTH exome AF: 0.717

GnomAD4 exome AF: 0.718 AC: 1049259 AN: 1461876 Hom.: 377508 Cov.: 87 AF XY: 0.720 AC XY: 523291 AN XY: 727240

Gnomad4 AFR exome AF: 0.791

Gnomad4 AMR exome AF: 0.802

Gnomad4 ASJ exome AF: 0.758

Gnomad4 EAS exome AF: 0.610

Gnomad4 SAS exome AF: 0.789

Gnomad4 FIN exome AF: 0.658

Gnomad4 NFE exome AF: 0.712

Gnomad4 OTH exome AF: 0.719

GnomAD4 genome AF: 0.736 AC: 112035 AN: 152142 Hom.: 41399 Cov.: 33 AF XY: 0.735 AC XY: 54705 AN XY: 74388

Gnomad4 AFR AF: 0.790

Gnomad4 AMR AF: 0.774

Gnomad4 ASJ AF: 0.757

Gnomad4 EAS AF: 0.641

Gnomad4 SAS AF: 0.789

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.710

Gnomad4 OTH AF: 0.738

Alfa AF: 0.718 Hom.: 56744

Bravo AF: 0.748

EpiCase AF: 0.712

EpiControl AF: 0.714

ClinVar

Significance: Benign

Submissions summary: Benign:5

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	Mar 24, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Cataract 33 Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 27, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.045
DANN	Benign	0.39

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: rs6080718; hg19: chr20-17474968; COSMIC: COSV64900694;