3-133449980-G-A

Variant names:

• chr3-133449980-G-A
• rs9833847
• NM_003571.4:c.730-323G>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.730-323G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (818 hom., cov: 16)
• Consequence: BFSP2 NM_003571.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.09

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=-1.0).
• BP6: Variant 3-133449980-G-A is Benign according to our data. Variant chr3-133449980-G-A is described in ClinVar as [Benign]. Clinvar id is 1276319.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BFSP2	NM_003571.4	c.730-323G>A		intron_variant	Intron 3 of 6	ENST00000302334.3	NP_003562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BFSP2	ENST00000302334.3	c.730-323G>A		intron_variant	Intron 3 of 6	1	NM_003571.4	ENSP00000304987.2
BFSP2-AS1	ENST00000515542.1	n.168-1085C>T		intron_variant	Intron 2 of 4	1
BFSP2	ENST00000511434.1	n.196-323G>A		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.150 AC: 12690 AN: 84852 Hom.: 815 Cov.: 16

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.0700

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0289

Gnomad EAS AF: 0.0827

Gnomad SAS AF: 0.0525

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.0435

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.150 AC: 12712 AN: 84926 Hom.: 818 Cov.: 16 AF XY: 0.152 AC XY: 6053 AN XY: 39804

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.0289

Gnomad4 EAS AF: 0.0825

Gnomad4 SAS AF: 0.0516

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.129

Alfa AF: 0.241 Hom.: 169

Asia WGS AF: 0.0800 AC: 277 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 24, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.39
DANN	Benign	0.29

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: rs9833847; hg19: chr3-133168824;