3-133404892-G-A

Variant names:

• chr3-133404892-G-A
• rs1153876
• NM_003571.4:c.489+4320G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003571.4(BFSP2):​c.489+4320G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,022 control chromosomes in the GnomAD database, including 20,074 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 0.51 (20071 hom., cov: 32)
  • Exomes 𝑓: 0.69 (3 hom.)
• Consequence: BFSP2 NM_003571.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.925
• Publications: 2 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003571.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BFSP2	NM_003571.4	MANE Select	c.489+4320G>A		intron	N/A	NP_003562.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BFSP2	ENST00000302334.3	TSL:1 MANE Select	c.489+4320G>A		intron	N/A	ENSP00000304987.2
	BFSP2	ENST00000511140.1	TSL:3	n.111+4320G>A		intron	N/A
	BFSP2	ENST00000513441.1	TSL:5	n.*18G>A		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77868 AN: 151888 Hom.: 20052 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.522

GnomAD4 exome AF: 0.688 AC: 11 AN: 16 Hom.: 3 Cov.: 0 AF XY: 0.667 AC XY: 8 AN XY: 12

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.700 AC: 7 AN: 10

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.513 AC: 77926 AN: 152006 Hom.: 20071 Cov.: 32 AF XY: 0.514 AC XY: 38209 AN XY: 74276

African (AFR) AF: 0.452 AC: 18722 AN: 41450

American (AMR) AF: 0.504 AC: 7703 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1954 AN: 3468

East Asian (EAS) AF: 0.545 AC: 2815 AN: 5162

South Asian (SAS) AF: 0.534 AC: 2568 AN: 4810

European-Finnish (FIN) AF: 0.570 AC: 6021 AN: 10556

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.537 AC: 36517 AN: 67972

Other (OTH) AF: 0.524 AC: 1106 AN: 2110

Alfa AF: 0.428 Hom.: 1540

Bravo AF: 0.502

Asia WGS AF: 0.519 AC: 1809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.3
DANN	Benign	0.83
PhyloP100		0.93
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1153876; hg19: chr3-133123736;