chr3-133448273-G-A

Position:

• chr3-133448273-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003571.4(BFSP2):​c.573-216G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,196 control chromosomes in the GnomAD database, including 798 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (798 hom., cov: 32)
• Consequence: BFSP2 NM_003571.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.852

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 3-133448273-G-A is Benign according to our data. Variant chr3-133448273-G-A is described in ClinVar as [Benign]. Clinvar id is 1229325.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BFSP2	NM_003571.4	c.573-216G>A		intron_variant		ENST00000302334.3	NP_003562.1
BFSP2-AS1	NR_135277.1	n.381-2698C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BFSP2	ENST00000302334.3	c.573-216G>A		intron_variant		1	NM_003571.4	ENSP00000304987	P1
BFSP2-AS1	ENST00000515542.1	n.282+508C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15339 AN: 152078 Hom.: 798 Cov.: 32

Gnomad AFR AF: 0.0770

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0886

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0999

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.101 AC: 15336 AN: 152196 Hom.: 798 Cov.: 32 AF XY: 0.102 AC XY: 7606 AN XY: 74400

Gnomad4 AFR AF: 0.0769

Gnomad4 AMR AF: 0.0884

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0999

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.115

Alfa AF: 0.107 Hom.: 174

Bravo AF: 0.100

Asia WGS AF: 0.124 AC: 431 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.52
DANN	Benign	0.61

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: rs75186898; hg19: chr3-133167117;