rs839232

chr3-58035099-T-A

Variant summary

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

The NM_001457.4(FLNB):c.292+26243T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 152,054 control chromosomes in the GnomAD database, including 43,691 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 0.75 (43691 hom., cov: 31)
• Consequence: FLNB NM_001457.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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 = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLNB	NM_001457.4	c.292+26243T>A		intron_variant		ENST00000295956.9
FLNB	NM_001164317.2	c.292+26243T>A		intron_variant
FLNB	NM_001164318.2	c.292+26243T>A		intron_variant
FLNB	NM_001164319.2	c.292+26243T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLNB	ENST00000295956.9	c.292+26243T>A		intron_variant		1	NM_001457.4	A1

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113807 AN: 151936 Hom.: 43633 Cov.: 31

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.764

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

GnomAD4 genome AF: 0.749 AC: 113922 AN: 152054 Hom.: 43691 Cov.: 31 AF XY: 0.754 AC XY: 56024 AN XY: 74314

Gnomad4 AFR AF: 0.880

Gnomad4 AMR AF: 0.754

Gnomad4 ASJ AF: 0.858

Gnomad4 EAS AF: 0.946

Gnomad4 SAS AF: 0.863

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.766

Alfa AF: 0.704 Hom.: 4810

Bravo AF: 0.765

Asia WGS AF: 0.887 AC: 3085 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	0.018
Dann	Benign	0.50

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: rs839232; hg19: chr3-58020826;