20-17494572-C-T

Position:

• chr20-17494572-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001195.5(BFSP1):​c.1500G>A​(p.Ala500=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,613,960 control chromosomes in the GnomAD database, including 55,506 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6243 hom., cov: 32)
  • Exomes 𝑓: 0.25 (49263 hom.)
• Consequence: BFSP1 NM_001195.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.104

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 20-17494572-C-T is Benign according to our data. Variant chr20-17494572-C-T is described in ClinVar as [Benign]. Clinvar id is 257614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-17494572-C-T is described in Lovd as [Benign]. Variant chr20-17494572-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.104 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BFSP1	NM_001195.5	c.1500G>A	p.Ala500=	synonymous_variant	8/8	ENST00000377873.8	NP_001186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BFSP1	ENST00000377873.8	c.1500G>A	p.Ala500=	synonymous_variant	8/8	1	NM_001195.5	ENSP00000367104	P1
BFSP1	ENST00000377868.6	c.1125G>A	p.Ala375=	synonymous_variant	8/8	1		ENSP00000367099
BFSP1	ENST00000536626.7	c.1083G>A	p.Ala361=	synonymous_variant	9/9	2		ENSP00000442522

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42851 AN: 151984 Hom.: 6218 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.289

GnomAD3 exomes AF: 0.289 AC: 72649 AN: 251314 Hom.: 11032 AF XY: 0.287 AC XY: 39033 AN XY: 135842

Gnomad AFR exome AF: 0.335

Gnomad AMR exome AF: 0.349

Gnomad ASJ exome AF: 0.290

Gnomad EAS exome AF: 0.405

Gnomad SAS exome AF: 0.354

Gnomad FIN exome AF: 0.221

Gnomad NFE exome AF: 0.242

Gnomad OTH exome AF: 0.268

GnomAD4 exome AF: 0.255 AC: 372396 AN: 1461856 Hom.: 49263 Cov.: 50 AF XY: 0.258 AC XY: 187327 AN XY: 727232

Gnomad4 AFR exome AF: 0.344

Gnomad4 AMR exome AF: 0.340

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.394

Gnomad4 SAS exome AF: 0.354

Gnomad4 FIN exome AF: 0.222

Gnomad4 NFE exome AF: 0.236

Gnomad4 OTH exome AF: 0.270

GnomAD4 genome AF: 0.282 AC: 42922 AN: 152104 Hom.: 6243 Cov.: 32 AF XY: 0.284 AC XY: 21142 AN XY: 74340

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.288

Alfa AF: 0.255 Hom.: 8372

Bravo AF: 0.287

Asia WGS AF: 0.346 AC: 1206 AN: 3478

EpiCase AF: 0.241

EpiControl AF: 0.241

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 02, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Cataract 33 Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 27, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.7
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs6136118; hg19: chr20-17475217; COSMIC: COSV64900543;