chr20-17494336-C-T

Variant names:

• chr20-17494336-C-T
• NM_001195.5:c.1736G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001195.5(BFSP1):​c.1736G>A​(p.Gly579Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BFSP1 NM_001195.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.647

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17654154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BFSP1	NM_001195.5	c.1736G>A	p.Gly579Asp	missense_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.1736G>A	p.Gly579Asp	missense_variant	Exon 8 of 8	1	NM_001195.5	ENSP00000367104.3
BFSP1	ENST00000377868.6	c.1361G>A	p.Gly454Asp	missense_variant	Exon 8 of 8	1		ENSP00000367099.2
BFSP1	ENST00000536626.7	c.1319G>A	p.Gly440Asp	missense_variant	Exon 9 of 9	2		ENSP00000442522.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461818 Hom.: 0 Cov.: 54 AF XY: 0.00000138 AC XY: 1 AN XY: 727216

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.9	M;.;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.6	N;D;D
REVEL	Benign	0.15
Sift	Benign	0.060	T;T;T
Sift4G	Benign	0.16	T;.;D
Polyphen		0.25	B;P;.
Vest4		0.23
MutPred		0.37		Gain of loop (P = 0.1069);.;.;
MVP		0.75
MPC		0.47
ClinPred		0.81	D
GERP RS		4.4
Varity_R		0.11
gMVP		0.10

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-17474981; COSMIC: COSV105309560;