20-17494323-T-C

Variant names:

• chr20-17494323-T-C
• rs6080718
• NM_001195.5:c.1749A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001195.5(BFSP1):​c.1749A>G​(p.Pro583Pro) 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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BFSP1	NM_001195.5	c.1749A>G	p.Pro583Pro	synonymous_variant	Exon 8 of 8	ENST00000377873.8	NP_001186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BFSP1	ENST00000377873.8	c.1749A>G	p.Pro583Pro	synonymous_variant	Exon 8 of 8	1	NM_001195.5	ENSP00000367104.3
BFSP1	ENST00000377868.6	c.1374A>G	p.Pro458Pro	synonymous_variant	Exon 8 of 8	1		ENSP00000367099.2
BFSP1	ENST00000536626.7	c.1332A>G	p.Pro444Pro	synonymous_variant	Exon 9 of 9	2		ENSP00000442522.1

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

GnomAD2 exomes AF: 0.731 AC: 183735 AN: 251436 AF XY: 0.730

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 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 AC: 26495 AN: 33480

Gnomad4 AMR exome AF: 0.802 AC: 35857 AN: 44724

Gnomad4 ASJ exome AF: 0.758 AC: 19810 AN: 26136

Gnomad4 EAS exome AF: 0.610 AC: 24216 AN: 39700

Gnomad4 SAS exome AF: 0.789 AC: 68033 AN: 86258

Gnomad4 FIN exome AF: 0.658 AC: 35123 AN: 53404

Gnomad4 NFE exome AF: 0.712 AC: 792133 AN: 1112010

Gnomad4 Remaining exome AF: 0.719 AC: 43423 AN: 60396

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 AC: 0.789528 AN: 0.789528

Gnomad4 AMR AF: 0.774 AC: 0.774274 AN: 0.774274

Gnomad4 ASJ AF: 0.757 AC: 0.757488 AN: 0.757488

Gnomad4 EAS AF: 0.641 AC: 0.641001 AN: 0.641001

Gnomad4 SAS AF: 0.789 AC: 0.789266 AN: 0.789266

Gnomad4 FIN AF: 0.663 AC: 0.663269 AN: 0.663269

Gnomad4 NFE AF: 0.710 AC: 0.709707 AN: 0.709707

Gnomad4 OTH AF: 0.738 AC: 0.738389 AN: 0.738389

Alfa AF: 0.721 Hom.: 71239

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

Cataract 33 Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.045
DANN	Benign	0.39
Mutation Taster		=100/0	polymorphism (auto)

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;