3-133448962-GT-GTTTT

Variant names:

• chr3-133448962-G-GTTT
• rs11454142
• NM_003571.4:c.729+324_729+326dupTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003571.4(BFSP2):​c.729+324_729+326dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000591 in 169,216 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000059 (0 hom.)
• Consequence: BFSP2 NM_003571.4 intron
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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+324_729+326dupTTT		intron	N/A	NP_003562.1	Q13515
	BFSP2-AS1	NR_135276.2		n.344-70_344-68dupAAA		intron	N/A
	BFSP2-AS1	NR_135277.2		n.344-3390_344-3388dupAAA		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+318insTTT		intron	N/A	ENSP00000304987.2	Q13515
	BFSP2-AS1	ENST00000515542.1	TSL:1	n.168-68_168-67insAAA		intron	N/A
	BFSP2-AS1	ENST00000833663.1		n.263-21628_263-21627insAAA		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000591 AC: 1 AN: 169216 Hom.: 0 Cov.: 0 AF XY: 0.0000111 AC XY: 1 AN XY: 90012

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 5254

American (AMR) AF: 0.00 AC: 0 AN: 7314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4594

East Asian (EAS) AF: 0.00 AC: 0 AN: 8680

South Asian (SAS) AF: 0.00 AC: 0 AN: 27834

European-Finnish (FIN) AF: 0.000127 AC: 1 AN: 7862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 650

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 98010

Other (OTH) AF: 0.00 AC: 0 AN: 9018

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11454142; hg19: chr3-133167806;