rs9809315

Positions:

• chr3-58064538-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.293-12508C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 151,910 control chromosomes in the GnomAD database, including 5,983 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 0.27 (5983 hom., cov: 31)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLNB	NM_001457.4	c.293-12508C>T		intron_variant		ENST00000295956.9	NP_001448.2
FLNB	NM_001164317.2	c.293-12508C>T		intron_variant			NP_001157789.1
FLNB	NM_001164318.2	c.293-12508C>T		intron_variant			NP_001157790.1
FLNB	NM_001164319.2	c.293-12508C>T		intron_variant			NP_001157791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLNB	ENST00000295956.9	c.293-12508C>T		intron_variant		1	NM_001457.4	ENSP00000295956	A1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40991 AN: 151792 Hom.: 5974 Cov.: 31

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.0145

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.270 AC: 41024 AN: 151910 Hom.: 5983 Cov.: 31 AF XY: 0.264 AC XY: 19631 AN XY: 74226

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.0143

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.282

Alfa AF: 0.302 Hom.: 9470

Bravo AF: 0.266

Asia WGS AF: 0.127 AC: 445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.34
DANN	Benign	0.30

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: rs9809315; hg19: chr3-58050265;