rs931099

chr3-133460736-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003571.4(BFSP2):c.892-6092C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,076 control chromosomes in the GnomAD database, including 10,027 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 0.34 (10027 hom., cov: 32)
• Consequence: BFSP2 NM_003571.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.613

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BFSP2	NM_003571.4	c.892-6092C>T		intron_variant		ENST00000302334.3
BFSP2-AS1	NR_135277.1	n.246-5273G>A		intron_variant, non_coding_transcript_variant
BFSP2	XM_017007315.2	c.892-6092C>T		intron_variant
BFSP2-AS1	NR_135276.1	n.246-5273G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BFSP2	ENST00000302334.3	c.892-6092C>T		intron_variant		1	NM_003571.4	P1
BFSP2	ENST00000510039.1	n.43-6098C>T		intron_variant, non_coding_transcript_variant		3
BFSP2	ENST00000511434.1	n.358-6092C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51875 AN: 151958 Hom.: 10027 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.341 AC: 51889 AN: 152076 Hom.: 10027 Cov.: 32 AF XY: 0.343 AC XY: 25469 AN XY: 74354

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.575

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.370

Alfa AF: 0.403 Hom.: 25878

Bravo AF: 0.341

Asia WGS AF: 0.530 AC: 1842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.43
Dann	Benign	0.70

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: rs931099; hg19: chr3-133179580;