3-133449982-A-AAGGAAGGAAGG

Variant names:

• chr3-133449982-A-AAGGAAGGAAGG
• rs1212404887
• NM_003571.4:c.730-320_730-319insGGAAGGAAGGA

Variant summary

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

The NM_003571.4(BFSP2):​c.730-320_730-319insGGAAGGAAGGA variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00029 (0 hom., cov: 0)
• Consequence: BFSP2 NM_003571.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• 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 0 ACMG points.

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.730-320_730-319insGGAAGGAAGGA		intron	N/A	NP_003562.1	Q13515
	BFSP2-AS1	NR_135276.2		n.344-1088_344-1087insCCTTCCTTCCT		intron	N/A
	BFSP2-AS1	NR_135277.2		n.344-4408_344-4407insCCTTCCTTCCT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BFSP2	ENST00000302334.3	TSL:1 MANE Select	c.730-321_730-320insAGGAAGGAAGG		intron	N/A	ENSP00000304987.2	Q13515
	BFSP2-AS1	ENST00000515542.1	TSL:1	n.168-1088_168-1087insCCTTCCTTCCT		intron	N/A
	BFSP2	ENST00000511434.1	TSL:3	n.196-321_196-320insAGGAAGGAAGG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000290 AC: 25 AN: 86278 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000292

Gnomad AMI AF: 0.00161

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00143

Gnomad EAS AF: 0.000360

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000275

Gnomad OTH AF: 0.00184

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

GnomAD4 genome AF: 0.000289 AC: 25 AN: 86384 Hom.: 0 Cov.: 0 AF XY: 0.000249 AC XY: 10 AN XY: 40146

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

African (AFR) AF: 0.000291 AC: 6 AN: 20654

American (AMR) AF: 0.00 AC: 0 AN: 8380

Ashkenazi Jewish (ASJ) AF: 0.00143 AC: 3 AN: 2096

East Asian (EAS) AF: 0.000361 AC: 1 AN: 2770

South Asian (SAS) AF: 0.00 AC: 0 AN: 2000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5036

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 154

European-Non Finnish (NFE) AF: 0.000275 AC: 12 AN: 43562

Other (OTH) AF: 0.00180 AC: 2 AN: 1110

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000000459854), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0070

Splicing

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

Other links and lift over

dbSNP: rs1212404887; hg19: chr3-133168826;