chr20-17494924-T-C

Position:

• chr20-17494924-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000377873.8(BFSP1):​c.1148A>G​(p.Asn383Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000772 in 1,614,132 control chromosomes in the GnomAD database, including 17 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 0.0015 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00070 (12 hom.)
• Consequence: BFSP1 ENST00000377873.8 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.57

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003048122).
• BP6: Variant 20-17494924-T-C is Benign according to our data. Variant chr20-17494924-T-C is described in ClinVar as [Benign]. Clinvar id is 474088.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00149 (227/152254) while in subpopulation EAS AF= 0.0287 (149/5184). AF 95% confidence interval is 0.025. There are 5 homozygotes in gnomad4. There are 114 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BFSP1	NM_001195.5	c.1148A>G	p.Asn383Ser	missense_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.1148A>G	p.Asn383Ser	missense_variant	8/8	1	NM_001195.5	ENSP00000367104	P1
BFSP1	ENST00000377868.6	c.773A>G	p.Asn258Ser	missense_variant	8/8	1		ENSP00000367099
BFSP1	ENST00000536626.7	c.731A>G	p.Asn244Ser	missense_variant	9/9	2		ENSP00000442522

Frequencies

GnomAD3 genomes AF: 0.00148 AC: 225 AN: 152136 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00150

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.00620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00256 AC: 643 AN: 251346 Hom.: 15 AF XY: 0.00245 AC XY: 333 AN XY: 135876

Gnomad AFR exome AF: 0.000861

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.0294

Gnomad SAS exome AF: 0.00186

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000792

Gnomad OTH exome AF: 0.00293

GnomAD4 exome AF: 0.000697 AC: 1019 AN: 1461878 Hom.: 12 Cov.: 34 AF XY: 0.000759 AC XY: 552 AN XY: 727238

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.0000894

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0128

Gnomad4 SAS exome AF: 0.00243

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000791

Gnomad4 OTH exome AF: 0.00326

GnomAD4 genome AF: 0.00149 AC: 227 AN: 152254 Hom.: 5 Cov.: 33 AF XY: 0.00153 AC XY: 114 AN XY: 74458

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0287

Gnomad4 SAS AF: 0.00600

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.000829 Hom.: 2

Bravo AF: 0.00130

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00242 AC: 294

Asia WGS AF: 0.0270 AC: 92 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cataract 33 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 06, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.2
DANN	Benign	0.52
DEOGEN2	Benign	0.086	T;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.57	T;T;T
MetaRNN	Benign	0.0030	T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	-0.14	N;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.42	N;N;N
REVEL	Benign	0.076
Sift	Benign	0.10	T;T;T
Sift4G	Benign	0.45	T;.;T
Polyphen		0.0	B;B;.
Vest4		0.036
MVP		0.58
MPC		0.060
ClinPred		0.0032	T
GERP RS		0.28
Varity_R		0.030
gMVP		0.096

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: rs150798461; hg19: chr20-17475569;