3-133437848-C-T

Variant names:

• chr3-133437848-C-T
• rs6762405
• NM_003571.4:c.490-9469C>T

Variant summary

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

The NM_003571.4(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 NM_003571.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438
• Publications: 4 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-AS1 (HGNC:28425): (BFSP2 antisense RNA 1)

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BFSP2	NM_003571.4	c.490-9469C>T		intron_variant	Intron 1 of 6	ENST00000302334.3	NP_003562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BFSP2	ENST00000302334.3	c.490-9469C>T		intron_variant	Intron 1 of 6	1	NM_003571.4	ENSP00000304987.2

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

African (AFR) AF: 0.651 AC: 26945 AN: 41400

American (AMR) AF: 0.252 AC: 3842 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1199 AN: 3468

East Asian (EAS) AF: 0.362 AC: 1866 AN: 5152

South Asian (SAS) AF: 0.329 AC: 1582 AN: 4814

European-Finnish (FIN) AF: 0.219 AC: 2315 AN: 10586

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16940 AN: 67938

Other (OTH) AF: 0.366 AC: 773 AN: 2112

Alfa AF: 0.284 Hom.: 27102

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
PhyloP100		-0.44
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: rs6762405; hg19: chr3-133156692;