rs139124891

Variant names:

• chr20-17494947-C-A
• rs139124891
• NM_001195.5:c.1125G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-17494947-C-A
• chr20-17494947-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001195.5(BFSP1):​c.1125G>T​(p.Glu375Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,614,188 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (19 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (21 hom.)
• Consequence: BFSP1 NM_001195.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.82
• Publications: 2 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027216077).
• BP6: Variant 20-17494947-C-A is Benign according to our data. Variant chr20-17494947-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 474087.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0105 (1594/152300) while in subpopulation AFR AF = 0.0364 (1514/41552). AF 95% confidence interval is 0.0349. There are 19 homozygotes in GnomAd4. There are 748 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BFSP1	NM_001195.5	MANE Select	c.1125G>T	p.Glu375Asp	missense	Exon 8 of 8	NP_001186.1	Q12934-1
	BFSP1	NM_001424338.1		c.1017G>T	p.Glu339Asp	missense	Exon 7 of 7	NP_001411267.1
	BFSP1	NM_001278607.2		c.792G>T	p.Glu264Asp	missense	Exon 8 of 8	NP_001265536.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BFSP1	ENST00000377873.8	TSL:1 MANE Select	c.1125G>T	p.Glu375Asp	missense	Exon 8 of 8	ENSP00000367104.3	Q12934-1
	BFSP1	ENST00000377868.6	TSL:1	c.750G>T	p.Glu250Asp	missense	Exon 8 of 8	ENSP00000367099.2	Q12934-2
	BFSP1	ENST00000929672.1		c.1017G>T	p.Glu339Asp	missense	Exon 7 of 7	ENSP00000599731.1

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1591 AN: 152182 Hom.: 19 Cov.: 33

Gnomad AFR AF: 0.0365

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00379

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00765

GnomAD2 exomes AF: 0.00279 AC: 699 AN: 250720 AF XY: 0.00200

Gnomad AFR exome AF: 0.0395

Gnomad AMR exome AF: 0.00127

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000354

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00103 AC: 1511 AN: 1461888 Hom.: 21 Cov.: 34 AF XY: 0.000833 AC XY: 606 AN XY: 727244

African (AFR) AF: 0.0382 AC: 1278 AN: 33480

American (AMR) AF: 0.00154 AC: 69 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1112012

Other (OTH) AF: 0.00214 AC: 129 AN: 60396

GnomAD4 genome AF: 0.0105 AC: 1594 AN: 152300 Hom.: 19 Cov.: 33 AF XY: 0.0100 AC XY: 748 AN XY: 74470

African (AFR) AF: 0.0364 AC: 1514 AN: 41552

American (AMR) AF: 0.00379 AC: 58 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68026

Other (OTH) AF: 0.00757 AC: 16 AN: 2114

Alfa AF: 0.00313 Hom.: 21

Bravo AF: 0.0114

ESP6500AA AF: 0.0365 AC: 161

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00352 AC: 427

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Cataract 33 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.68	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.8
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.11
Sift	Benign	0.12	T
Sift4G	Benign	0.16	T
Polyphen		0.91	P
Vest4		0.089
MutPred		0.35		Gain of MoRF binding (P = 0.1098)
MVP		0.94
MPC		0.37
ClinPred		0.010	T
GERP RS		4.3
Varity_R		0.17
gMVP		0.19
Mutation Taster		=75/25	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: rs139124891; hg19: chr20-17475592; COSMIC: COSV99061013;