20-17496947-C-T

Position:

• chr20-17496947-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000377873.8(BFSP1):​c.1033G>A​(p.Gly345Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,533,522 control chromosomes in the GnomAD database, including 48,505 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3972 hom., cov: 32)
  • Exomes 𝑓: 0.25 (44533 hom.)
• Consequence: BFSP1 ENST00000377873.8 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.631

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025340319).
• BP6: Variant 20-17496947-C-T is Benign according to our data. Variant chr20-17496947-C-T is described in ClinVar as [Benign]. Clinvar id is 257612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-17496947-C-T is described in Lovd as [Benign]. Variant chr20-17496947-C-T is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BFSP1	NM_001195.5	c.1033G>A	p.Gly345Ser	missense_variant	7/8	ENST00000377873.8	NP_001186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BFSP1	ENST00000377873.8	c.1033G>A	p.Gly345Ser	missense_variant	7/8	1	NM_001195.5	ENSP00000367104	P1
BFSP1	ENST00000377868.6	c.658G>A	p.Gly220Ser	missense_variant	7/8	1		ENSP00000367099
BFSP1	ENST00000536626.7	c.616G>A	p.Gly206Ser	missense_variant	8/9	2		ENSP00000442522

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32367 AN: 151702 Hom.: 3964 Cov.: 32

Gnomad AFR AF: 0.0934

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.239

GnomAD3 exomes AF: 0.263 AC: 37007 AN: 140546 Hom.: 5313 AF XY: 0.269 AC XY: 19986 AN XY: 74392

Gnomad AFR exome AF: 0.0874

Gnomad AMR exome AF: 0.309

Gnomad ASJ exome AF: 0.268

Gnomad EAS exome AF: 0.394

Gnomad SAS exome AF: 0.339

Gnomad FIN exome AF: 0.220

Gnomad NFE exome AF: 0.236

Gnomad OTH exome AF: 0.254

GnomAD4 exome AF: 0.249 AC: 343671 AN: 1381702 Hom.: 44533 Cov.: 32 AF XY: 0.252 AC XY: 172104 AN XY: 681624

Gnomad4 AFR exome AF: 0.0890

Gnomad4 AMR exome AF: 0.304

Gnomad4 ASJ exome AF: 0.272

Gnomad4 EAS exome AF: 0.390

Gnomad4 SAS exome AF: 0.350

Gnomad4 FIN exome AF: 0.223

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.255

GnomAD4 genome AF: 0.213 AC: 32394 AN: 151820 Hom.: 3972 Cov.: 32 AF XY: 0.217 AC XY: 16108 AN XY: 74196

Gnomad4 AFR AF: 0.0934

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.238

Alfa AF: 0.244 Hom.: 11354

Bravo AF: 0.209

TwinsUK AF: 0.229 AC: 848

ALSPAC AF: 0.247 AC: 952

ESP6500AA AF: 0.0833 AC: 362

ESP6500EA AF: 0.212 AC: 1781

ExAC AF: 0.135 AC: 12081

Asia WGS AF: 0.325 AC: 1132 AN: 3478

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

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
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.10
DANN	Benign	0.51
DEOGEN2	Benign	0.039	T;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0041	N
LIST_S2	Benign	0.53	T;T;T
MetaRNN	Benign	0.0025	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.17	N;.;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.79	N;N;N
REVEL	Benign	0.043
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.80	T;.;T
Polyphen		0.0010	B;B;.
Vest4		0.020
MPC		0.076
ClinPred		0.00012	T
GERP RS		-5.0
Varity_R		0.024
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6080719; hg19: chr20-17477592; COSMIC: COSV64899826;