20-17493942-G-A

Variant names:

• chr20-17493942-G-A
• rs74488569
• NM_001195.5:c.*132C>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.*132C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0233 in 821,954 control chromosomes in the GnomAD database, including 444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (89 hom., cov: 32)
  • Exomes 𝑓: 0.024 (355 hom.)
• Consequence: BFSP1 NM_001195.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.201
• Publications: 4 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 (BayesDel_noAF=-0.85).
• BP6: Variant 20-17493942-G-A is Benign according to our data. Variant chr20-17493942-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1213460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0993 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.*132C>T		3_prime_UTR	Exon 8 of 8	NP_001186.1	Q12934-1
	BFSP1	NM_001424338.1		c.*132C>T		3_prime_UTR	Exon 7 of 7	NP_001411267.1
	BFSP1	NM_001278607.2		c.*132C>T		3_prime_UTR	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.*132C>T		3_prime_UTR	Exon 8 of 8	ENSP00000367104.3	Q12934-1
	BFSP1	ENST00000377868.6	TSL:1	c.*132C>T		3_prime_UTR	Exon 8 of 8	ENSP00000367099.2	Q12934-2
	BFSP1	ENST00000929672.1		c.*132C>T		3_prime_UTR	Exon 7 of 7	ENSP00000599731.1

Frequencies

GnomAD3 genomes AF: 0.0210 AC: 3199 AN: 152150 Hom.: 89 Cov.: 32

Gnomad AFR AF: 0.00466

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0575

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.0276

Gnomad FIN AF: 0.0207

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0174

Gnomad OTH AF: 0.0153

GnomAD4 exome AF: 0.0238 AC: 15957 AN: 669686 Hom.: 355 Cov.: 9 AF XY: 0.0237 AC XY: 8097 AN XY: 341948

African (AFR) AF: 0.00345 AC: 58 AN: 16798

American (AMR) AF: 0.0546 AC: 1143 AN: 20926

Ashkenazi Jewish (ASJ) AF: 0.000397 AC: 6 AN: 15132

East Asian (EAS) AF: 0.0990 AC: 3334 AN: 33692

South Asian (SAS) AF: 0.0265 AC: 1234 AN: 46544

European-Finnish (FIN) AF: 0.0214 AC: 824 AN: 38522

Middle Eastern (MID) AF: 0.00201 AC: 8 AN: 3984

European-Non Finnish (NFE) AF: 0.0187 AC: 8637 AN: 460776

Other (OTH) AF: 0.0214 AC: 713 AN: 33312

GnomAD4 genome AF: 0.0210 AC: 3195 AN: 152268 Hom.: 89 Cov.: 32 AF XY: 0.0223 AC XY: 1660 AN XY: 74452

African (AFR) AF: 0.00464 AC: 193 AN: 41560

American (AMR) AF: 0.0574 AC: 878 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.107 AC: 551 AN: 5168

South Asian (SAS) AF: 0.0274 AC: 132 AN: 4816

European-Finnish (FIN) AF: 0.0207 AC: 220 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0174 AC: 1187 AN: 68024

Other (OTH) AF: 0.0151 AC: 32 AN: 2116

Alfa AF: 0.0206 Hom.: 74

Bravo AF: 0.0226

Asia WGS AF: 0.0530 AC: 183 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	-0.85
CADD	Benign	3.3
DANN	Benign	0.59
PhyloP100		0.20
Mutation Taster		=100/0	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: rs74488569; hg19: chr20-17474587;