rs2281207

Variant names:

• chr20-17509088-G-A
• rs2281207
• NM_001195.5:c.628-92C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-17509088-G-A
• chr20-17509088-G-C
• chr20-17509088-G-T

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.628-92C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 901,020 control chromosomes in the GnomAD database, including 14,527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2789 hom., cov: 33)
  • Exomes 𝑓: 0.16 (11738 hom.)
• Consequence: BFSP1 NM_001195.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.08
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 20-17509088-G-A is Benign according to our data. Variant chr20-17509088-G-A is described in ClinVar as Benign. ClinVar VariationId is 1287293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 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.628-92C>T		intron	N/A	NP_001186.1	Q12934-1
	BFSP1	NM_001424338.1		c.627+2888C>T		intron	N/A	NP_001411267.1
	BFSP1	NM_001278607.2		c.295-92C>T		intron	N/A	NP_001265536.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BFSP1	ENST00000377873.8	TSL:1 MANE Select	c.628-92C>T		intron	N/A	ENSP00000367104.3	Q12934-1
	BFSP1	ENST00000377868.6	TSL:1	c.253-92C>T		intron	N/A	ENSP00000367099.2	Q12934-2
	BFSP1	ENST00000929672.1		c.627+2888C>T		intron	N/A	ENSP00000599731.1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26884 AN: 152026 Hom.: 2779 Cov.: 33

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.0957

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.159 AC: 119153 AN: 748878 Hom.: 11738 AF XY: 0.164 AC XY: 61207 AN XY: 374182

African (AFR) AF: 0.221 AC: 3640 AN: 16480

American (AMR) AF: 0.212 AC: 2803 AN: 13228

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 2314 AN: 14622

East Asian (EAS) AF: 0.425 AC: 11614 AN: 27298

South Asian (SAS) AF: 0.311 AC: 13102 AN: 42150

European-Finnish (FIN) AF: 0.109 AC: 3253 AN: 29900

Middle Eastern (MID) AF: 0.213 AC: 882 AN: 4148

European-Non Finnish (NFE) AF: 0.133 AC: 75312 AN: 566120

Other (OTH) AF: 0.178 AC: 6233 AN: 34932

GnomAD4 genome AF: 0.177 AC: 26923 AN: 152142 Hom.: 2789 Cov.: 33 AF XY: 0.181 AC XY: 13474 AN XY: 74384

African (AFR) AF: 0.211 AC: 8750 AN: 41500

American (AMR) AF: 0.194 AC: 2970 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 554 AN: 3472

East Asian (EAS) AF: 0.439 AC: 2255 AN: 5138

South Asian (SAS) AF: 0.340 AC: 1639 AN: 4820

European-Finnish (FIN) AF: 0.0957 AC: 1015 AN: 10606

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9205 AN: 67992

Other (OTH) AF: 0.187 AC: 395 AN: 2112

Alfa AF: 0.0673 Hom.: 88

Bravo AF: 0.184

Asia WGS AF: 0.401 AC: 1393 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.037
DANN	Benign	0.63
PhyloP100		-2.1
Mutation Taster		=94/6	polymorphism (auto)

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: rs2281207; hg19: chr20-17489733; COSMIC: COSV107478821; COSMIC: COSV107478821;