3-58013259-C-T

Position:

• chr3-58013259-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001457.4(FLNB):​c.292+4403C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,020 control chromosomes in the GnomAD database, including 9,124 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (9124 hom., cov: 32)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53

Genes affected

FLNB (HGNC:3755): (filamin B) This gene encodes a member of the filamin family. The encoded protein interacts with glycoprotein Ib alpha as part of the process to repair vascular injuries. The platelet glycoprotein Ib complex includes glycoprotein Ib alpha, and it binds the actin cytoskeleton. Mutations in this gene have been found in several conditions: atelosteogenesis type 1 and type 3; boomerang dysplasia; autosomal dominant Larsen syndrome; and spondylocarpotarsal synostosis syndrome. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Nov 2009]

FLNB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLNB	NM_001457.4	c.292+4403C>T		intron_variant		ENST00000295956.9	NP_001448.2
FLNB	NM_001164317.2	c.292+4403C>T		intron_variant			NP_001157789.1
FLNB	NM_001164318.2	c.292+4403C>T		intron_variant			NP_001157790.1
FLNB	NM_001164319.2	c.292+4403C>T		intron_variant			NP_001157791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLNB	ENST00000295956.9	c.292+4403C>T		intron_variant		1	NM_001457.4	ENSP00000295956.5

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50085 AN: 151902 Hom.: 9103 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.330 AC: 50146 AN: 152020 Hom.: 9124 Cov.: 32 AF XY: 0.333 AC XY: 24711 AN XY: 74312

Gnomad4 AFR AF: 0.460

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.323

Alfa AF: 0.270 Hom.: 11915

Bravo AF: 0.338

Asia WGS AF: 0.482 AC: 1673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	13
DANN	Benign	0.56

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: rs9828717; hg19: chr3-57998986;