3-133448962-G-GT

Position:

• chr3-133448962-G-GT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003571.4(BFSP2):​c.729+326dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 316,450 control chromosomes in the GnomAD database, including 2,996 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2250 hom., cov: 29)
  • Exomes 𝑓: 0.12 (746 hom.)
• Consequence: BFSP2 NM_003571.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.475

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 -10 ACMG points.

• BP6: Variant 3-133448962-G-GT is Benign according to our data. Variant chr3-133448962-G-GT is described in ClinVar as [Benign]. Clinvar id is 1229983.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BFSP2	NM_003571.4	c.729+326dup		intron_variant		ENST00000302334.3	NP_003562.1
BFSP2-AS1	NR_135277.1	n.381-3388_381-3387insA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BFSP2	ENST00000302334.3	c.729+326dup		intron_variant		1	NM_003571.4	ENSP00000304987	P1
BFSP2-AS1	ENST00000515542.1	n.168-68_168-67insA		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24764 AN: 150566 Hom.: 2241 Cov.: 29

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0658

Gnomad EAS AF: 0.0677

Gnomad SAS AF: 0.0390

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.118 AC: 19553 AN: 165772 Hom.: 746 Cov.: 0 AF XY: 0.108 AC XY: 9562 AN XY: 88214

Gnomad4 AFR exome AF: 0.219

Gnomad4 AMR exome AF: 0.0902

Gnomad4 ASJ exome AF: 0.0668

Gnomad4 EAS exome AF: 0.0661

Gnomad4 SAS exome AF: 0.0446

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.165 AC: 24796 AN: 150678 Hom.: 2250 Cov.: 29 AF XY: 0.162 AC XY: 11927 AN XY: 73554

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.0658

Gnomad4 EAS AF: 0.0676

Gnomad4 SAS AF: 0.0389

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.136

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 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs11454142; hg19: chr3-133167806;