Genetic Variant NM_003571.4:c.489+8808T>A (chr3-133409380-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003571.4(BFSP2):c.489+8808T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,080 control chromosomes in the GnomAD database, including 14,110 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.41 ( 14110 hom., cov: 32)

Consequence

BFSP2
NM_003571.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.16

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

cataract 12 multiple types
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
early-onset non-syndromic cataract
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
early-onset lamellar cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
early-onset sutural cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
pulverulent cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

BFSP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BFSP2	NM_003571.4 link	c.489+8808T>A		intron_variant	Intron 1 of 6	ENST00000302334.3	NP_003562.1	Q13515
BFSP2	XM_017007315.2 link	c.489+8808T>A		intron_variant	Intron 1 of 5		XP_016862804.1	Q13515

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BFSP2	ENST00000302334.3 link	c.489+8808T>A		intron_variant	Intron 1 of 6	1	NM_003571.4	ENSP00000304987.2		Q13515
BFSP2	ENST00000511140.1 link	n.112-2908T>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.413

AC:

62812

AN:

151962

Hom.:

14107

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.321

Gnomad AMR

AF:

0.447

Gnomad ASJ

AF:

0.526

Gnomad EAS

AF:

0.498

Gnomad SAS

AF:

0.498

Gnomad FIN

AF:

0.548

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.482

Gnomad OTH

AF:

0.441

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.413

AC:

62839

AN:

152080

Hom.:

14110

Cov.:

AF XY:

0.418

AC XY:

31092

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.224

AC:

9284

AN:

41482

American (AMR)

AF:

0.447

AC:

6832

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.526

AC:

1824

AN:

3470

East Asian (EAS)

AF:

0.498

AC:

2577

AN:

5178

South Asian (SAS)

AF:

0.498

AC:

2400

AN:

4824

European-Finnish (FIN)

AF:

0.548

AC:

5788

AN:

10564

Middle Eastern (MID)

AF:

0.469

AC:

138

AN:

294

European-Non Finnish (NFE)

AF:

0.482

AC:

32771

AN:

67962

Other (OTH)

AF:

0.441

AC:

932

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1833

3666

5500

7333

9166

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.453

Hom.:

2066

Bravo

AF:

0.394

Asia WGS

AF:

0.455

AC:

1585

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.7

(source)

DANN

Benign

0.90

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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NM_003571.4:c.489+8808T>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over