rs9834312

chr3-58096982-G-Achr3-58096982-G-Cchr3-58096982-G-T

Variant summary

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

The NM_001457.4(FLNB):c.984+764G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,020 control chromosomes in the GnomAD database, including 15,323 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 0.43 (15323 hom., cov: 32)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLNB	NM_001457.4	c.984+764G>A		intron_variant		ENST00000295956.9
FLNB	NM_001164317.2	c.984+764G>A		intron_variant
FLNB	NM_001164318.2	c.984+764G>A		intron_variant
FLNB	NM_001164319.2	c.984+764G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLNB	ENST00000295956.9	c.984+764G>A		intron_variant		1	NM_001457.4	A1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64658 AN: 151902 Hom.: 15299 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.426 AC: 64731 AN: 152020 Hom.: 15323 Cov.: 32 AF XY: 0.434 AC XY: 32237 AN XY: 74276

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.922

Gnomad4 SAS AF: 0.596

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.416

Alfa AF: 0.401 Hom.: 2215

Bravo AF: 0.443

Asia WGS AF: 0.751 AC: 2609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.077
Dann	Benign	0.65

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: rs9834312; hg19: chr3-58082709;