NM_001195.5:c.1749A>C

Variant names:

• chr20-17494323-T-G
• rs6080718
• NM_001195.5:c.1749A>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001195.5(BFSP1):​c.1749A>C​(p.Pro583Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P583P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BFSP1 NM_001195.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.31
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 20-17494323-T-G is Benign according to our data. Variant chr20-17494323-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2652210.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-5.31 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BFSP1	NM_001195.5	MANE Select	c.1749A>C	p.Pro583Pro	synonymous	Exon 8 of 8	NP_001186.1
	BFSP1	NM_001424338.1		c.1641A>C	p.Pro547Pro	synonymous	Exon 7 of 7	NP_001411267.1
	BFSP1	NM_001278607.2		c.1416A>C	p.Pro472Pro	synonymous	Exon 8 of 8	NP_001265536.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BFSP1	ENST00000377873.8	TSL:1 MANE Select	c.1749A>C	p.Pro583Pro	synonymous	Exon 8 of 8	ENSP00000367104.3
	BFSP1	ENST00000377868.6	TSL:1	c.1374A>C	p.Pro458Pro	synonymous	Exon 8 of 8	ENSP00000367099.2
	BFSP1	ENST00000536626.7	TSL:2	c.1332A>C	p.Pro444Pro	synonymous	Exon 9 of 9	ENSP00000442522.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 87

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

BFSP1: PM2:Supporting, BP4, BP7

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.033
DANN	Benign	0.38
PhyloP100		-5.3

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: rs6080718; hg19: chr20-17474968;