3-133448962-GT-GTT

Variant names:

• chr3-133448962-G-GT
• rs11454142
• NM_003571.4:c.729+326dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003571.4(BFSP2):​c.729+326dupT 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
• Publications: 0 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-AS1 (HGNC:28425): (BFSP2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003571.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BFSP2	NM_003571.4	MANE Select	c.729+326dupT		intron	N/A	NP_003562.1	Q13515
	BFSP2-AS1	NR_135276.2		n.344-68dupA		intron	N/A
	BFSP2-AS1	NR_135277.2		n.344-3388dupA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BFSP2	ENST00000302334.3	TSL:1 MANE Select	c.729+317_729+318insT		intron	N/A	ENSP00000304987.2	Q13515
	BFSP2-AS1	ENST00000515542.1	TSL:1	n.168-68_168-67insA		intron	N/A
	BFSP2-AS1	ENST00000833663.1		n.263-21628_263-21627insA		intron	N/A

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

African (AFR) AF: 0.219 AC: 1134 AN: 5168

American (AMR) AF: 0.0902 AC: 642 AN: 7120

Ashkenazi Jewish (ASJ) AF: 0.0668 AC: 300 AN: 4492

East Asian (EAS) AF: 0.0661 AC: 561 AN: 8488

South Asian (SAS) AF: 0.0446 AC: 1213 AN: 27196

European-Finnish (FIN) AF: 0.168 AC: 1298 AN: 7716

Middle Eastern (MID) AF: 0.0645 AC: 41 AN: 636

European-Non Finnish (NFE) AF: 0.138 AC: 13300 AN: 96102

Other (OTH) AF: 0.120 AC: 1064 AN: 8854

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

African (AFR) AF: 0.245 AC: 10062 AN: 41018

American (AMR) AF: 0.121 AC: 1829 AN: 15124

Ashkenazi Jewish (ASJ) AF: 0.0658 AC: 227 AN: 3452

East Asian (EAS) AF: 0.0676 AC: 345 AN: 5104

South Asian (SAS) AF: 0.0389 AC: 182 AN: 4684

European-Finnish (FIN) AF: 0.189 AC: 1964 AN: 10368

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.145 AC: 9800 AN: 67636

Other (OTH) AF: 0.136 AC: 285 AN: 2090

Alfa AF: 0.0453 Hom.: 54

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.47
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: rs11454142; hg19: chr3-133167806;