rs1623879

chr3-58041470-A-G

Variant summary

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

The NM_001457.4(FLNB):c.292+32614A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 151,784 control chromosomes in the GnomAD database, including 4,850 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 0.21 (4850 hom., cov: 31)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLNB	NM_001457.4	c.292+32614A>G		intron_variant		ENST00000295956.9
FLNB	NM_001164317.2	c.292+32614A>G		intron_variant
FLNB	NM_001164318.2	c.292+32614A>G		intron_variant
FLNB	NM_001164319.2	c.292+32614A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLNB	ENST00000295956.9	c.292+32614A>G		intron_variant		1	NM_001457.4	A1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31702 AN: 151666 Hom.: 4836 Cov.: 31

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0952

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.209 AC: 31762 AN: 151784 Hom.: 4850 Cov.: 31 AF XY: 0.212 AC XY: 15726 AN XY: 74190

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.0952

Gnomad4 OTH AF: 0.188

Alfa AF: 0.123 Hom.: 1612

Bravo AF: 0.234

Asia WGS AF: 0.296 AC: 1029 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.5
Dann	Benign	0.63

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: rs1623879; hg19: chr3-58027197;