rs1197310

Positions:

• chr3-133409380-T-A
• chr3-133409380-T-G

Variant summary

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

The NM_003571.4(BFSP2):​c.489+8808T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,080 control chromosomes in the GnomAD database, including 14,110 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 0.41 (14110 hom., cov: 32)
• Consequence: BFSP2 NM_003571.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BFSP2	NM_003571.4	c.489+8808T>A		intron_variant		ENST00000302334.3	NP_003562.1
BFSP2	XM_017007315.2	c.489+8808T>A		intron_variant			XP_016862804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BFSP2	ENST00000302334.3	c.489+8808T>A		intron_variant		1	NM_003571.4	ENSP00000304987	P1
BFSP2	ENST00000511140.1	n.112-2908T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62812 AN: 151962 Hom.: 14107 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.441

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

GnomAD4 genome AF: 0.413 AC: 62839 AN: 152080 Hom.: 14110 Cov.: 32 AF XY: 0.418 AC XY: 31092 AN XY: 74342

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.441

Alfa AF: 0.453 Hom.: 2066

Bravo AF: 0.394

Asia WGS AF: 0.455 AC: 1585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.7
DANN	Benign	0.90

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: rs1197310; hg19: chr3-133128224;