Variant chr3-133448519-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_003571.4(BFSP2):c.603G>A(p.Ala201=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 1,613,420 control chromosomes in the GnomAD database, including 282,437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 19696 hom., cov: 32)

Exomes 𝑓: 0.59 ( 262741 hom. )

Consequence

BFSP2
NM_003571.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.161

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:28425): (BFSP2 antisense RNA 1)

BFSP2-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 3-133448519-G-A is Benign according to our data. Variant chr3-133448519-G-A is described in ClinVar as [Benign]. Clinvar id is 1164247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-133448519-G-A is described in Lovd as [Benign]. Variant chr3-133448519-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.161 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BFSP2	NM_003571.4 linkuse as main transcript	c.603G>A	p.Ala201=	synonymous_variant	3/7	ENST00000302334.3
BFSP2-AS1	NR_135277.1 linkuse as main transcript	n.381-2944C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BFSP2	ENST00000302334.3 linkuse as main transcript	c.603G>A	p.Ala201=	synonymous_variant	3/7	1	NM_003571.4	P1
BFSP2-AS1	ENST00000515542.1 linkuse as main transcript	n.282+262C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.469

AC:

71279

AN:

151912

Hom.:

19695

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.791

Gnomad AMR

AF:

0.439

Gnomad ASJ

AF:

0.582

Gnomad EAS

AF:

0.583

Gnomad SAS

AF:

0.616

Gnomad FIN

AF:

0.539

Gnomad MID

AF:

0.598

Gnomad NFE

AF:

0.617

Gnomad OTH

AF:

0.500

GnomAD3 exomes

AF:

0.539

AC:

135182

AN:

251004

Hom.:

38870

AF XY:

0.557

AC XY:

75611

AN XY:

135658

show subpopulations

Gnomad AFR exome

AF:

0.155

Gnomad AMR exome

AF:

0.349

Gnomad ASJ exome

AF:

0.554

Gnomad EAS exome

AF:

0.596

Gnomad SAS exome

AF:

0.618

Gnomad FIN exome

AF:

0.539

Gnomad NFE exome

AF:

0.618

Gnomad OTH exome

AF:

0.561

GnomAD4 exome

AF:

0.593

AC:

866158

AN:

1461388

Hom.:

262741

Cov.:

AF XY:

0.596

AC XY:

433386

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.149

Gnomad4 AMR exome

AF:

0.359

Gnomad4 ASJ exome

AF:

0.560

Gnomad4 EAS exome

AF:

0.559

Gnomad4 SAS exome

AF:

0.618

Gnomad4 FIN exome

AF:

0.547

Gnomad4 NFE exome

AF:

0.619

Gnomad4 OTH exome

AF:

0.567

GnomAD4 genome

AF:

0.469

AC:

71287

AN:

152032

Hom.:

19696

Cov.:

AF XY:

0.468

AC XY:

34779

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.168

Gnomad4 AMR

AF:

0.438

Gnomad4 ASJ

AF:

0.582

Gnomad4 EAS

AF:

0.583

Gnomad4 SAS

AF:

0.618

Gnomad4 FIN

AF:

0.539

Gnomad4 NFE

AF:

0.617

Gnomad4 OTH

AF:

0.500

Alfa

AF:

0.574

Hom.:

41590

Bravo

AF:

0.443

Asia WGS

AF:

0.553

AC:

1924

AN:

3478

EpiCase

AF:

0.615

EpiControl

AF:

0.618

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cataract 12 multiple types

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 27, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

9.7

DANN

Benign

0.83

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