rs4854585

Variant names:

• chr3-133418440-G-A
• rs4854585
• NM_003571.4:c.489+17868G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-133418440-G-A
• chr3-133418440-G-C
• chr3-133418440-G-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.489+17868G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 151,924 control chromosomes in the GnomAD database, including 25,394 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 0.57 (25394 hom., cov: 31)
• Consequence: BFSP2 NM_003571.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.664
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BFSP2	NM_003571.4	c.489+17868G>A		intron_variant	Intron 1 of 6	ENST00000302334.3	NP_003562.1
BFSP2	XM_017007315.2	c.489+17868G>A		intron_variant	Intron 1 of 5		XP_016862804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BFSP2	ENST00000302334.3	c.489+17868G>A		intron_variant	Intron 1 of 6	1	NM_003571.4	ENSP00000304987.2

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85820 AN: 151808 Hom.: 25376 Cov.: 31

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.902

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.565 AC: 85867 AN: 151924 Hom.: 25394 Cov.: 31 AF XY: 0.571 AC XY: 42413 AN XY: 74238

African (AFR) AF: 0.405 AC: 16789 AN: 41444

American (AMR) AF: 0.686 AC: 10492 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2244 AN: 3468

East Asian (EAS) AF: 0.902 AC: 4651 AN: 5156

South Asian (SAS) AF: 0.702 AC: 3383 AN: 4818

European-Finnish (FIN) AF: 0.589 AC: 6211 AN: 10542

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40063 AN: 67910

Other (OTH) AF: 0.591 AC: 1240 AN: 2098

Alfa AF: 0.594 Hom.: 44789

Bravo AF: 0.567

Asia WGS AF: 0.752 AC: 2613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.58
DANN	Benign	0.87
PhyloP100		-0.66
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: rs4854585; hg19: chr3-133137284;