Variant 20-17494323-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1

The NM_001195.5(BFSP1):c.1749A>T(p.Pro583=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000227 in 1,614,080 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Benign.

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

BFSP1
NM_001195.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -5.31

Variant links:

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]

BFSP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 20-17494323-T-A is Benign according to our data. Variant chr20-17494323-T-A is described in ClinVar as [Benign]. Clinvar id is 1166147.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-17494323-T-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-5.31 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00134 (204/152196) while in subpopulation AFR AF= 0.00477 (198/41520). AF 95% confidence interval is 0.00422. There are 0 homozygotes in gnomad4. There are 85 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BFSP1	NM_001195.5 linkuse as main transcript	c.1749A>T	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 linkuse as main transcript	c.1749A>T	p.Pro583=	synonymous_variant	8/8	1	NM_001195.5	ENSP00000367104	P1	Q12934-1
BFSP1	ENST00000377868.6 linkuse as main transcript	c.1374A>T	p.Pro458=	synonymous_variant	8/8	1		ENSP00000367099		Q12934-2
BFSP1	ENST00000536626.7 linkuse as main transcript	c.1332A>T	p.Pro444=	synonymous_variant	9/9	2		ENSP00000442522		Q12934-3

Frequencies

GnomAD3 genomes

AF:

0.00134

AC:

204

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00478

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000410

AC:

103

AN:

251436

Hom.:

AF XY:

0.000265

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00566

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000111

AC:

162

AN:

1461884

Hom.:

Cov.:

AF XY:

0.0000825

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00352

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.00134

AC:

204

AN:

152196

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00477

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00000456

Hom.:

56744

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cataract 33

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 11, 2023

- -

BFSP1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 10, 2021

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

-0.87

CADD

Benign

0.031

DANN

Benign

0.43

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over