rs2023224

Positions:

• chr20-17517124-G-A

Variant summary

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

The NM_001195.5(BFSP1):​c.439-2308C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 803,654 control chromosomes in the GnomAD database, including 61,488 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 (12910 hom., cov: 33)
  • Exomes 𝑓: 0.38 (48578 hom.)
• Consequence: BFSP1 NM_001195.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.789

Genes affected

BFSP1 (HGNC:1040): (beaded filament structural protein 1) This gene encodes a lens-specific intermediate filament-like protein named filensin. The encoded protein is expressed in lens fiber cells after differentiation has begun. This protein functions as a component of the beaded filament which is a cytoskeletal structure found in lens fiber cells. Mutations in this gene are the cause of autosomal recessive cortical juvenile-onset cataract. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

RPS27AP2 (HGNC:16572): (RPS27A pseudogene 2)

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 (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BFSP1	NM_001195.5	c.439-2308C>T		intron_variant		ENST00000377873.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BFSP1	ENST00000377873.8	c.439-2308C>T		intron_variant		1	NM_001195.5	P1
RPS27AP2	ENST00000457576.1	n.282G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61938 AN: 151944 Hom.: 12879 Cov.: 33

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.401

GnomAD4 exome AF: 0.383 AC: 249469 AN: 651592 Hom.: 48578 Cov.: 7 AF XY: 0.384 AC XY: 135901 AN XY: 353788

Gnomad4 AFR exome AF: 0.486

Gnomad4 AMR exome AF: 0.384

Gnomad4 ASJ exome AF: 0.334

Gnomad4 EAS exome AF: 0.406

Gnomad4 SAS exome AF: 0.427

Gnomad4 FIN exome AF: 0.359

Gnomad4 NFE exome AF: 0.371

Gnomad4 OTH exome AF: 0.397

GnomAD4 genome AF: 0.408 AC: 62016 AN: 152062 Hom.: 12910 Cov.: 33 AF XY: 0.407 AC XY: 30228 AN XY: 74320

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.406

Alfa AF: 0.399 Hom.: 1511

Bravo AF: 0.409

Asia WGS AF: 0.407 AC: 1416 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	1.6
DANN	Benign	0.70

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: rs2023224; hg19: chr20-17497769;