NM_001195.5:c.1033G>A

Variant names:

• chr20-17496947-C-T
• rs6080719
• NM_001195.5:c.1033G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001195.5(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. 15/21 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 NM_001195.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.631
• Publications: 32 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=0.0025340319).
• BP6: Variant 20-17496947-C-T is Benign according to our data. Variant chr20-17496947-C-T is described in ClinVar as Benign. ClinVar VariationId is 257612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

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.1033G>A	p.Gly345Ser	missense	Exon 7 of 8	NP_001186.1	Q12934-1
	BFSP1	NM_001424338.1		c.925G>A	p.Gly309Ser	missense	Exon 6 of 7	NP_001411267.1
	BFSP1	NM_001278607.2		c.700G>A	p.Gly234Ser	missense	Exon 7 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.1033G>A	p.Gly345Ser	missense	Exon 7 of 8	ENSP00000367104.3	Q12934-1
	BFSP1	ENST00000377868.6	TSL:1	c.658G>A	p.Gly220Ser	missense	Exon 7 of 8	ENSP00000367099.2	Q12934-2
	BFSP1	ENST00000929672.1		c.925G>A	p.Gly309Ser	missense	Exon 6 of 7	ENSP00000599731.1

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

GnomAD2 exomes AF: 0.263 AC: 37007 AN: 140546 AF XY: 0.269

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 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

African (AFR) AF: 0.0890 AC: 2710 AN: 30434

American (AMR) AF: 0.304 AC: 9417 AN: 30946

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 6733 AN: 24786

East Asian (EAS) AF: 0.390 AC: 13438 AN: 34456

South Asian (SAS) AF: 0.350 AC: 26448 AN: 75600

European-Finnish (FIN) AF: 0.223 AC: 10985 AN: 49182

Middle Eastern (MID) AF: 0.257 AC: 1438 AN: 5604

European-Non Finnish (NFE) AF: 0.240 AC: 257878 AN: 1073380

Other (OTH) AF: 0.255 AC: 14624 AN: 57314

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

African (AFR) AF: 0.0934 AC: 3868 AN: 41394

American (AMR) AF: 0.273 AC: 4168 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 915 AN: 3468

East Asian (EAS) AF: 0.391 AC: 2008 AN: 5140

South Asian (SAS) AF: 0.360 AC: 1732 AN: 4810

European-Finnish (FIN) AF: 0.221 AC: 2328 AN: 10548

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16671 AN: 67902

Other (OTH) AF: 0.238 AC: 501 AN: 2104

Alfa AF: 0.239 Hom.: 15217

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.17	N
PhyloP100		-0.63
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.79	N
REVEL	Benign	0.043
Sift	Benign	1.0	T
Sift4G	Benign	0.80	T
Polyphen		0.0010	B
Vest4		0.020
MPC		0.076
ClinPred		0.00012	T
GERP RS		-5.0
Varity_R		0.024
gMVP		0.15
Mutation Taster		=97/3	polymorphism (auto)

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: rs6080719; hg19: chr20-17477592; COSMIC: COSV64899826;