20-17494947-C-A

Position:

chr20-17494947-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001195.5(BFSP1):c.1125G>T(p.Glu375Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,614,188 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 19 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 21 hom. )

Consequence

BFSP1
NM_001195.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.82

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027216077).

BP6

Variant 20-17494947-C-A is Benign according to our data. Variant chr20-17494947-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 474087.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1594/152300) while in subpopulation AFR AF= 0.0364 (1514/41552). AF 95% confidence interval is 0.0349. There are 19 homozygotes in gnomad4. There are 748 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BFSP1	NM_001195.5 linkuse as main transcript	c.1125G>T	p.Glu375Asp	missense_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.1125G>T	p.Glu375Asp	missense_variant	8/8	1	NM_001195.5	ENSP00000367104	P1	Q12934-1
BFSP1	ENST00000377868.6 linkuse as main transcript	c.750G>T	p.Glu250Asp	missense_variant	8/8	1		ENSP00000367099		Q12934-2
BFSP1	ENST00000536626.7 linkuse as main transcript	c.708G>T	p.Glu236Asp	missense_variant	9/9	2		ENSP00000442522		Q12934-3

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1591

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0365

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00379

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:

0.0000882

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00279

AC:

699

AN:

250720

Hom.:

AF XY:

0.00200

AC XY:

271

AN XY:

135584

show subpopulations

Gnomad AFR exome

AF:

0.0395

Gnomad AMR exome

AF:

0.00127

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00103

AC:

1511

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000833

AC XY:

606

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0382

Gnomad4 AMR exome

AF:

0.00154

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.00214

GnomAD4 genome

AF:

0.0105

AC:

1594

AN:

152300

Hom.:

Cov.:

AF XY:

0.0100

AC XY:

748

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0364

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00143

Hom.:

Bravo

AF:

0.0114

ESP6500AA

AF:

0.0365

AC:

161

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00352

AC:

427

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 25, 2020	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Cataract 33

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;.;.

Eigen

Benign

0.13

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.68

T;T;T

MetaRNN

Benign

0.0027

T;T;T

MetaSVM

Benign

-0.37

MutationAssessor

Uncertain

2.3

M;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.12

T;T;T

Sift4G

Benign

0.16

T;.;T

Polyphen

0.91

P;B;.

Vest4

0.089

MutPred

0.35

Gain of MoRF binding (P = 0.1098);.;.;

MVP

0.94

MPC

0.37

ClinPred

0.010

GERP RS

4.3

Varity_R

0.17

gMVP

0.19

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