20-17508949-C-T

Variant names:

• chr20-17508949-C-T
• rs140834233
• NM_001195.5:c.675G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001195.5(BFSP1):​c.675G>A​(p.Leu225Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,604,808 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (49 hom.)
• Consequence: BFSP1 NM_001195.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.19
• Publications: 5 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]

BFSP1 Gene-Disease associations (from GenCC):

• cataract 33

  Inheritance: AR, AD, SD Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• early-onset nuclear cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000294980 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 20-17508949-C-T is Benign according to our data. Variant chr20-17508949-C-T is described in ClinVar as Benign. ClinVar VariationId is 541142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.18 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0011 (168/152358) while in subpopulation EAS AF = 0.0232 (120/5166). AF 95% confidence interval is 0.0199. There are 3 homozygotes in GnomAd4. There are 83 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR,AD,SD gene

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.675G>A	p.Leu225Leu	synonymous	Exon 5 of 8	NP_001186.1
	BFSP1	NM_001278607.2		c.342G>A	p.Leu114Leu	synonymous	Exon 5 of 8	NP_001265536.1
	BFSP1	NM_001161705.2		c.300G>A	p.Leu100Leu	synonymous	Exon 5 of 8	NP_001155177.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BFSP1	ENST00000377873.8	TSL:1 MANE Select	c.675G>A	p.Leu225Leu	synonymous	Exon 5 of 8	ENSP00000367104.3
	BFSP1	ENST00000377868.6	TSL:1	c.300G>A	p.Leu100Leu	synonymous	Exon 5 of 8	ENSP00000367099.2
	BFSP1	ENST00000536626.7	TSL:2	c.258G>A	p.Leu86Leu	synonymous	Exon 6 of 9	ENSP00000442522.1

Frequencies

GnomAD3 genomes AF: 0.00110 AC: 168 AN: 152240 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0236

Gnomad SAS AF: 0.00289

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00229 AC: 541 AN: 235958 AF XY: 0.00229

Gnomad AFR exome AF: 0.0000668

Gnomad AMR exome AF: 0.000219

Gnomad ASJ exome AF: 0.000205

Gnomad EAS exome AF: 0.0219

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000251

Gnomad OTH exome AF: 0.00194

GnomAD4 exome AF: 0.00158 AC: 2291 AN: 1452450 Hom.: 49 Cov.: 31 AF XY: 0.00165 AC XY: 1194 AN XY: 722098

African (AFR) AF: 0.000241 AC: 8 AN: 33184

American (AMR) AF: 0.000230 AC: 10 AN: 43450

Ashkenazi Jewish (ASJ) AF: 0.000154 AC: 4 AN: 25968

East Asian (EAS) AF: 0.0420 AC: 1641 AN: 39092

South Asian (SAS) AF: 0.00446 AC: 375 AN: 84118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52454

Middle Eastern (MID) AF: 0.00366 AC: 21 AN: 5744

European-Non Finnish (NFE) AF: 0.000125 AC: 139 AN: 1108438

Other (OTH) AF: 0.00155 AC: 93 AN: 60002

GnomAD4 genome AF: 0.00110 AC: 168 AN: 152358 Hom.: 3 Cov.: 33 AF XY: 0.00111 AC XY: 83 AN XY: 74494

African (AFR) AF: 0.0000481 AC: 2 AN: 41592

American (AMR) AF: 0.000653 AC: 10 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.0232 AC: 120 AN: 5166

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68036

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.000406 Hom.: 0

Bravo AF: 0.00114

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cataract 33 Benign:1

Nov 28, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		3.2
Mutation Taster		=99/1	polymorphism

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: rs140834233; hg19: chr20-17489594; COSMIC: COSV64902548; COSMIC: COSV64902548;