rs2276737

Positions:

• chr3-133448519-G-A
• chr3-133448519-G-C
• chr3-133448519-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_003571.4(BFSP2):​c.603G>A​(p.Ala201=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 1,613,420 control chromosomes in the GnomAD database, including 282,437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.47 (19696 hom., cov: 32)
  • Exomes 𝑓: 0.59 (262741 hom.)
• Consequence: BFSP2 NM_003571.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.161

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 3-133448519-G-A is Benign according to our data. Variant chr3-133448519-G-A is described in ClinVar as [Benign]. Clinvar id is 1164247.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-133448519-G-A is described in Lovd as [Benign]. Variant chr3-133448519-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.161 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BFSP2	NM_003571.4	c.603G>A	p.Ala201=	synonymous_variant	3/7	ENST00000302334.3
BFSP2-AS1	NR_135277.1	n.381-2944C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BFSP2	ENST00000302334.3	c.603G>A	p.Ala201=	synonymous_variant	3/7	1	NM_003571.4	P1
BFSP2-AS1	ENST00000515542.1	n.282+262C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71279 AN: 151912 Hom.: 19695 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.500

GnomAD3 exomes AF: 0.539 AC: 135182 AN: 251004 Hom.: 38870 AF XY: 0.557 AC XY: 75611 AN XY: 135658

Gnomad AFR exome AF: 0.155

Gnomad AMR exome AF: 0.349

Gnomad ASJ exome AF: 0.554

Gnomad EAS exome AF: 0.596

Gnomad SAS exome AF: 0.618

Gnomad FIN exome AF: 0.539

Gnomad NFE exome AF: 0.618

Gnomad OTH exome AF: 0.561

GnomAD4 exome AF: 0.593 AC: 866158 AN: 1461388 Hom.: 262741 Cov.: 54 AF XY: 0.596 AC XY: 433386 AN XY: 727040

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.359

Gnomad4 ASJ exome AF: 0.560

Gnomad4 EAS exome AF: 0.559

Gnomad4 SAS exome AF: 0.618

Gnomad4 FIN exome AF: 0.547

Gnomad4 NFE exome AF: 0.619

Gnomad4 OTH exome AF: 0.567

GnomAD4 genome AF: 0.469 AC: 71287 AN: 152032 Hom.: 19696 Cov.: 32 AF XY: 0.468 AC XY: 34779 AN XY: 74316

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.500

Alfa AF: 0.574 Hom.: 41590

Bravo AF: 0.443

Asia WGS AF: 0.553 AC: 1924 AN: 3478

EpiCase AF: 0.615

EpiControl AF: 0.618

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cataract 12 multiple types Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 27, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.7
DANN	Benign	0.83

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: rs2276737; hg19: chr3-133167363; COSMIC: COSV56588646; COSMIC: COSV56588646;