3-133447559-A-G

Position:

• chr3-133447559-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003571.4(BFSP2):​c.572+160A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.933 in 152,214 control chromosomes in the GnomAD database, including 66,327 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.93 (66327 hom., cov: 30)
• Consequence: BFSP2 NM_003571.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.812

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-133447559-A-G is Benign according to our data. Variant chr3-133447559-A-G is described in ClinVar as [Benign]. Clinvar id is 1192357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BFSP2	NM_003571.4	c.572+160A>G		intron_variant		ENST00000302334.3	NP_003562.1
BFSP2-AS1	NR_135277.1	n.381-1984T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BFSP2	ENST00000302334.3	c.572+160A>G		intron_variant		1	NM_003571.4	ENSP00000304987	P1
BFSP2-AS1	ENST00000515542.1	n.282+1222T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.933 AC: 141894 AN: 152094 Hom.: 66279 Cov.: 30

Gnomad AFR AF: 0.902

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.936

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.939

Gnomad FIN AF: 0.955

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.960

Gnomad OTH AF: 0.940

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

GnomAD4 genome AF: 0.933 AC: 141998 AN: 152214 Hom.: 66327 Cov.: 30 AF XY: 0.931 AC XY: 69302 AN XY: 74426

Gnomad4 AFR AF: 0.903

Gnomad4 AMR AF: 0.879

Gnomad4 ASJ AF: 0.936

Gnomad4 EAS AF: 0.908

Gnomad4 SAS AF: 0.939

Gnomad4 FIN AF: 0.955

Gnomad4 NFE AF: 0.960

Gnomad4 OTH AF: 0.939

Alfa AF: 0.947 Hom.: 13930

Bravo AF: 0.924

Asia WGS AF: 0.903 AC: 3141 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Cataract 12 multiple types Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.70
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: rs7644197; hg19: chr3-133166403;