NM_001195.5:c.106_107delGCinsTT

Variant names:

• chr20-17531223-GC-AA
• rs886038419
• NM_001195.5:c.106_107delGCinsTT

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_001195.5(BFSP1):​c.106_107delGCinsTT​(p.Ala36Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. The variant is present in control chromosomes in GnomAd MNV project. The variant allele was found at a frequency of 0.00231 in 183 alleles, including 0 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A36S) has been classified as Likely benign.

• Frequency: GnomAD MNV: 𝑓 0.0023 Genomes: not found (cov: 33)
• Consequence: BFSP1 NM_001195.5 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: 0.793
• 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 -1 ACMG points.

• BP6: Variant 20-17531223-GC-AA is Benign according to our data. Variant chr20-17531223-GC-AA is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 257613.

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.106_107delGCinsTT	p.Ala36Phe	missense	N/A	NP_001186.1
	BFSP1	NM_001424338.1		c.106_107delGCinsTT	p.Ala36Phe	missense	N/A	NP_001411267.1
	BFSP1	NM_001278607.2		c.45-6316_45-6315delGCinsTT		intron	N/A	NP_001265536.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BFSP1	ENST00000377873.8	TSL:1 MANE Select	c.106_107delGCinsTT	p.Ala36Phe	missense	N/A	ENSP00000367104.3
	BFSP1	ENST00000377868.6	TSL:1	c.3-6316_3-6315delGCinsTT		intron	N/A	ENSP00000367099.2
	BFSP1	ENST00000536626.7	TSL:2	c.-40-6316_-40-6315delGCinsTT		intron	N/A	ENSP00000442522.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

GnomAD MNV AF: 0.00231 AC: 183 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	Cataract 33 (1)
-	1	-	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs886038419; hg19: chr20-17511868; COSMIC: COSV105309564;