rs1153876

Positions:

• chr3-133404892-G-A
• chr3-133404892-G-C
• chr3-133404892-G-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BFSP2	NM_003571.4	c.489+4320G>A		intron_variant		ENST00000302334.3	NP_003562.1
BFSP2	XM_017007315.2	c.489+4320G>A		intron_variant			XP_016862804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BFSP2	ENST00000302334.3	c.489+4320G>A		intron_variant		1	NM_003571.4	ENSP00000304987.2
BFSP2	ENST00000511140.1	n.111+4320G>A		intron_variant		3
BFSP2	ENST00000513441.1	n.*18G>A		downstream_gene_variant		5

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

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.700

Gnomad4 OTH exome AF: 1.00

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

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.545

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.537

Gnomad4 OTH AF: 0.524

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.3
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

Other links and lift over

dbSNP: rs1153876; hg19: chr3-133123736;