20-17493942-G-A

Position:

• chr20-17493942-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BFSP1	NM_001195.5	c.*132C>T		3_prime_UTR_variant	8/8	ENST00000377873.8	NP_001186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BFSP1	ENST00000377873	c.*132C>T		3_prime_UTR_variant	8/8	1	NM_001195.5	ENSP00000367104.3
BFSP1	ENST00000377868	c.*132C>T		3_prime_UTR_variant	8/8	1		ENSP00000367099.2
BFSP1	ENST00000536626	c.*132C>T		3_prime_UTR_variant	9/9	2		ENSP00000442522.1

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

Gnomad4 AFR exome AF: 0.00345

Gnomad4 AMR exome AF: 0.0546

Gnomad4 ASJ exome AF: 0.000397

Gnomad4 EAS exome AF: 0.0990

Gnomad4 SAS exome AF: 0.0265

Gnomad4 FIN exome AF: 0.0214

Gnomad4 NFE exome AF: 0.0187

Gnomad4 OTH exome AF: 0.0214

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

Gnomad4 AFR AF: 0.00464

Gnomad4 AMR AF: 0.0574

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.0274

Gnomad4 FIN AF: 0.0207

Gnomad4 NFE AF: 0.0174

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.0181 Hom.: 8

Bravo AF: 0.0226

Asia WGS AF: 0.0530 AC: 183 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.3
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs74488569; hg19: chr20-17474587;