rs143850362

Variant names:

• chr20-17531193-C-A
• rs143850362
• NM_001195.5:c.137G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-17531193-C-A
• chr20-17531193-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001195.5(BFSP1):​c.137G>T​(p.Gly46Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000026 in 1,152,586 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G46W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: BFSP1 NM_001195.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.83
• Publications: 0 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.137G>T	p.Gly46Val	missense	Exon 1 of 8	NP_001186.1
	BFSP1	NM_001424338.1		c.137G>T	p.Gly46Val	missense	Exon 1 of 7	NP_001411267.1
	BFSP1	NM_001278607.2		c.45-6285G>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.137G>T	p.Gly46Val	missense	Exon 1 of 8	ENSP00000367104.3
	BFSP1	ENST00000377868.6	TSL:1	c.3-6285G>T		intron	N/A	ENSP00000367099.2
	BFSP1	ENST00000536626.7	TSL:2	c.-40-6285G>T		intron	N/A	ENSP00000442522.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000260 AC: 3 AN: 1152586 Hom.: 0 Cov.: 31 AF XY: 0.00000179 AC XY: 1 AN XY: 557982

African (AFR) AF: 0.00 AC: 0 AN: 23126

American (AMR) AF: 0.00 AC: 0 AN: 10890

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15502

East Asian (EAS) AF: 0.00 AC: 0 AN: 25646

South Asian (SAS) AF: 0.00 AC: 0 AN: 41878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3162

European-Non Finnish (NFE) AF: 0.00000312 AC: 3 AN: 960184

Other (OTH) AF: 0.00 AC: 0 AN: 46068

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D
Eigen	Benign	0.047
Eigen_PC	Benign	0.031
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.77	T
M_CAP	Pathogenic	0.95	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.8
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.52
Sift	Benign	0.22	T
Sift4G	Benign	0.14	T
Polyphen		0.85	P
Vest4		0.36
MutPred		0.55		Loss of catalytic residue at G46 (P = 0.0322)
MVP		0.94
MPC		2.1
ClinPred		0.95	D
GERP RS		1.6
PromoterAI		-0.26	Neutral
Varity_R		0.085
gMVP		0.32
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs143850362; hg19: chr20-17511838;