3-133472541-C-A

Position:

chr3-133472541-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000302334.3(BFSP2):c.1220C>A(p.Ala407Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0435 in 1,612,172 control chromosomes in the GnomAD database, including 1,686 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 137 hom., cov: 33)

Exomes 𝑓: 0.044 ( 1549 hom. )

Consequence

BFSP2
ENST00000302334.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.09

Variant links:

Genes affected

BFSP2 (HGNC:1041): (beaded filament structural protein 2) More than 99% of the vertebrate ocular lens is comprised of terminally differentiated lens fiber cells. Two lens-specific intermediate filament-like proteins, the protein product of this gene (phakinin), and filensin, are expressed only after fiber cell differentiation has begun. Both proteins are found in a structurally unique cytoskeletal element that is referred to as the beaded filament (BF). Mutations in this gene have been associated with juvenile-onset, progressive cataracts and Dowling-Meara epidermolysis bullosa simplex. [provided by RefSeq, Jun 2009]

BFSP2 links:

BFSP2-AS1 (HGNC:):

BFSP2-AS1 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=0.007096857).

BP6

Variant 3-133472541-C-A is Benign according to our data. Variant chr3-133472541-C-A is described in ClinVar as [Benign]. Clinvar id is 259089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
BFSP2	NM_003571.4 linkuse as main transcript	c.1220C>A	p.Ala407Asp	missense_variant	6/7	ENST00000302334.3	NP_003562.1
BFSP2-AS1	NR_135277.1 linkuse as main transcript	n.246-17078G>T		intron_variant, non_coding_transcript_variant
BFSP2	XM_017007315.2 linkuse as main transcript	c.1220C>A	p.Ala407Asp	missense_variant	6/6		XP_016862804.1
BFSP2-AS1	NR_135276.1 linkuse as main transcript	n.246-17078G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
BFSP2	ENST00000302334.3 linkuse as main transcript	c.1220C>A	p.Ala407Asp	missense_variant	6/7	1	NM_003571.4	ENSP00000304987	P1
BFSP2	ENST00000503047.1 linkuse as main transcript	n.200C>A		non_coding_transcript_exon_variant	1/2	2
BFSP2	ENST00000510039.1 linkuse as main transcript	n.365C>A		non_coding_transcript_exon_variant	3/4	3
BFSP2	ENST00000511434.1 linkuse as main transcript			downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0413

AC:

6287

AN:

152212

Hom.:

134

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0357

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0355

Gnomad ASJ

AF:

0.0691

Gnomad EAS

AF:

0.0233

Gnomad SAS

AF:

0.0586

Gnomad FIN

AF:

0.0461

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0437

Gnomad OTH

AF:

0.0622

GnomAD3 exomes

AF:

0.0447

AC:

10991

AN:

245866

Hom.:

297

AF XY:

0.0471

AC XY:

6298

AN XY:

133778

show subpopulations

Gnomad AFR exome

AF:

0.0353

Gnomad AMR exome

AF:

0.0269

Gnomad ASJ exome

AF:

0.0713

Gnomad EAS exome

AF:

0.0277

Gnomad SAS exome

AF:

0.0646

Gnomad FIN exome

AF:

0.0451

Gnomad NFE exome

AF:

0.0464

Gnomad OTH exome

AF:

0.0455

GnomAD4 exome

AF:

0.0438

AC:

63893

AN:

1459842

Hom.:

1549

Cov.:

AF XY:

0.0446

AC XY:

32420

AN XY:

726220

show subpopulations

Gnomad4 AFR exome

AF:

0.0361

Gnomad4 AMR exome

AF:

0.0275

Gnomad4 ASJ exome

AF:

0.0686

Gnomad4 EAS exome

AF:

0.0182

Gnomad4 SAS exome

AF:

0.0639

Gnomad4 FIN exome

AF:

0.0450

Gnomad4 NFE exome

AF:

0.0431

Gnomad4 OTH exome

AF:

0.0460

GnomAD4 genome

AF:

0.0414

AC:

6299

AN:

152330

Hom.:

137

Cov.:

AF XY:

0.0411

AC XY:

3064

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0358

Gnomad4 AMR

AF:

0.0355

Gnomad4 ASJ

AF:

0.0691

Gnomad4 EAS

AF:

0.0234

Gnomad4 SAS

AF:

0.0582

Gnomad4 FIN

AF:

0.0461

Gnomad4 NFE

AF:

0.0437

Gnomad4 OTH

AF:

0.0634

Alfa

AF:

0.0456

Hom.:

288

Bravo

AF:

0.0411

TwinsUK

AF:

0.0423

AC:

157

ALSPAC

AF:

0.0381

AC:

147

ESP6500AA

AF:

0.0325

AC:

143

ESP6500EA

AF:

0.0441

AC:

379

ExAC

AF:

0.0443

AC:

5372

Asia WGS

AF:

0.0470

AC:

164

AN:

3478

EpiCase

AF:

0.0481

EpiControl

AF:

0.0485

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Sep 07, 2018	- -

Cataract 12 multiple types

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 27, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

Eigen

Benign

0.15

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0071

MetaSVM

Benign

-0.48

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.98

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.31

Sift

Benign

0.59

Sift4G

Uncertain

0.047

Polyphen

0.92

Vest4

0.16

MPC

0.67

ClinPred

0.019

GERP RS

2.3

Varity_R

0.45

gMVP

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