3-133437848-C-T

Position:

• chr3-133437848-C-T

Variant summary

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

The ENST00000302334.3(BFSP2):​c.490-9469C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 151,944 control chromosomes in the GnomAD database, including 12,697 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 0.37 (12697 hom., cov: 32)
• Consequence: BFSP2 ENST00000302334.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438

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:28425): (BFSP2 antisense RNA 1)

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 (AFR) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BFSP2	NM_003571.4	c.490-9469C>T		intron_variant		ENST00000302334.3	NP_003562.1
BFSP2-AS1	NR_135277.1	n.551+7557G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BFSP2	ENST00000302334.3	c.490-9469C>T		intron_variant		1	NM_003571.4	ENSP00000304987	P1
BFSP2-AS1	ENST00000515542.1	n.453+7557G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55618 AN: 151826 Hom.: 12677 Cov.: 32

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.366 AC: 55682 AN: 151944 Hom.: 12697 Cov.: 32 AF XY: 0.364 AC XY: 27008 AN XY: 74260

Gnomad4 AFR AF: 0.651

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.366

Alfa AF: 0.264 Hom.: 10520

Bravo AF: 0.383

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.79

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: rs6762405; hg19: chr3-133156692;