chr20-17494065-C-G

Variant names:

• chr20-17494065-C-G
• rs41276390
• NM_001195.5:c.*9G>C

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.*9G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,604,540 control chromosomes in the GnomAD database, including 1,329 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.053 (701 hom., cov: 33)
  • Exomes 𝑓: 0.0081 (628 hom.)
• Consequence: BFSP1 NM_001195.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.196
• Publications: 3 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=-0.76).
• BP6: Variant 20-17494065-C-G is Benign according to our data. Variant chr20-17494065-C-G is described in ClinVar as [Benign]. Clinvar id is 1285829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BFSP1	NM_001195.5	c.*9G>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000377873.8	NP_001186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BFSP1	ENST00000377873.8	c.*9G>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_001195.5	ENSP00000367104.3
BFSP1	ENST00000377868.6	c.*9G>C		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000367099.2
BFSP1	ENST00000536626.7	c.*9G>C		3_prime_UTR_variant	Exon 9 of 9	2		ENSP00000442522.1

Frequencies

GnomAD3 genomes AF: 0.0532 AC: 8088 AN: 152138 Hom.: 695 Cov.: 33

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0215

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00393

Gnomad OTH AF: 0.0420

GnomAD2 exomes AF: 0.0152 AC: 3733 AN: 246014 AF XY: 0.0117

Gnomad AFR exome AF: 0.178

Gnomad AMR exome AF: 0.0106

Gnomad ASJ exome AF: 0.00560

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000141

Gnomad NFE exome AF: 0.00344

Gnomad OTH exome AF: 0.0100

GnomAD4 exome AF: 0.00811 AC: 11783 AN: 1452284 Hom.: 628 Cov.: 30 AF XY: 0.00721 AC XY: 5207 AN XY: 721922

African (AFR) AF: 0.189 AC: 6230 AN: 33018

American (AMR) AF: 0.0117 AC: 516 AN: 43954

Ashkenazi Jewish (ASJ) AF: 0.00389 AC: 100 AN: 25696

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.000837 AC: 71 AN: 84852

European-Finnish (FIN) AF: 0.000301 AC: 16 AN: 53166

Middle Eastern (MID) AF: 0.0190 AC: 109 AN: 5728

European-Non Finnish (NFE) AF: 0.00350 AC: 3877 AN: 1106252

Other (OTH) AF: 0.0144 AC: 864 AN: 59992

GnomAD4 genome AF: 0.0533 AC: 8112 AN: 152256 Hom.: 701 Cov.: 33 AF XY: 0.0515 AC XY: 3835 AN XY: 74452

African (AFR) AF: 0.178 AC: 7400 AN: 41522

American (AMR) AF: 0.0215 AC: 329 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00393 AC: 267 AN: 68016

Other (OTH) AF: 0.0421 AC: 89 AN: 2116

Alfa AF: 0.0171 Hom.: 49

Bravo AF: 0.0612

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.4
DANN	Benign	0.78
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: rs41276390; hg19: chr20-17474710; COSMIC: COSV105309604;