3-133410428-C-T

Position:

• chr3-133410428-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003571.4(BFSP2):​c.489+9856C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 270,462 control chromosomes in the GnomAD database, including 21,588 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (10895 hom., cov: 32)
  • Exomes 𝑓: 0.42 (10693 hom.)
• Consequence: BFSP2 NM_003571.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.49

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]

AFF4P1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BFSP2	NM_003571.4	c.489+9856C>T		intron_variant		ENST00000302334.3	NP_003562.1
BFSP2	XM_017007315.2	c.489+9856C>T		intron_variant			XP_016862804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BFSP2	ENST00000302334.3	c.489+9856C>T		intron_variant		1	NM_003571.4	ENSP00000304987.2
AFF4P1	ENST00000510575.1	n.474C>T		non_coding_transcript_exon_variant	1/1	6
BFSP2	ENST00000511140.1	n.112-1860C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53709 AN: 151876 Hom.: 10894 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.386

GnomAD4 exome AF: 0.421 AC: 49901 AN: 118468 Hom.: 10693 Cov.: 0 AF XY: 0.419 AC XY: 28670 AN XY: 68346

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.461

Gnomad4 ASJ exome AF: 0.464

Gnomad4 EAS exome AF: 0.465

Gnomad4 SAS exome AF: 0.397

Gnomad4 FIN exome AF: 0.481

Gnomad4 NFE exome AF: 0.421

Gnomad4 OTH exome AF: 0.436

GnomAD4 genome AF: 0.354 AC: 53736 AN: 151994 Hom.: 10895 Cov.: 32 AF XY: 0.359 AC XY: 26706 AN XY: 74308

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.386

Alfa AF: 0.394 Hom.: 3303

Bravo AF: 0.337

Asia WGS AF: 0.430 AC: 1496 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Benign	0.61

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: rs666067; hg19: chr3-133129272; COSMIC: COSV56591812;