rs2023224

Variant names:

• chr20-17517124-G-A
• rs2023224
• NM_001195.5:c.439-2308C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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)

ENSG00000294980 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BFSP1	NM_001195.5	MANE Select	c.439-2308C>T		intron	N/A	NP_001186.1
	BFSP1	NM_001424338.1		c.439-2308C>T		intron	N/A	NP_001411267.1
	BFSP1	NM_001278607.2		c.106-2308C>T		intron	N/A	NP_001265536.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BFSP1	ENST00000377873.8	TSL:1 MANE Select	c.439-2308C>T		intron	N/A	ENSP00000367104.3
	BFSP1	ENST00000377868.6	TSL:1	c.64-2308C>T		intron	N/A	ENSP00000367099.2
	RPS27AP2	ENST00000457576.1	TSL:6	n.282G>A		non_coding_transcript_exon	Exon 1 of 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

African (AFR) AF: 0.486 AC: 8889 AN: 18294

American (AMR) AF: 0.384 AC: 16738 AN: 43586

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 7096 AN: 21224

East Asian (EAS) AF: 0.406 AC: 14686 AN: 36190

South Asian (SAS) AF: 0.427 AC: 30014 AN: 70362

European-Finnish (FIN) AF: 0.359 AC: 14136 AN: 39390

Middle Eastern (MID) AF: 0.458 AC: 1198 AN: 2614

European-Non Finnish (NFE) AF: 0.371 AC: 143242 AN: 385970

Other (OTH) AF: 0.397 AC: 13470 AN: 33962

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

African (AFR) AF: 0.489 AC: 20269 AN: 41480

American (AMR) AF: 0.411 AC: 6276 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1195 AN: 3470

East Asian (EAS) AF: 0.378 AC: 1949 AN: 5152

South Asian (SAS) AF: 0.425 AC: 2051 AN: 4826

European-Finnish (FIN) AF: 0.353 AC: 3725 AN: 10560

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.372 AC: 25285 AN: 67972

Other (OTH) AF: 0.406 AC: 858 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.6
DANN	Benign	0.70
PhyloP100		0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2023224; hg19: chr20-17497769;