rs13079906

Positions:

chr3-58168450-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000295956.9(FLNB):c.7209G>A(p.Ser2403=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,612,022 control chromosomes in the GnomAD database, including 9,323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.088 ( 708 hom., cov: 33)

Exomes 𝑓: 0.10 ( 8615 hom. )

Consequence

FLNB
ENST00000295956.9 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.72

Variant links:

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 links:

FLNB-AS1 (HGNC:40239): (FLNB antisense RNA 1)

FLNB-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 3-58168450-G-A is Benign according to our data. Variant chr3-58168450-G-A is described in ClinVar as [Benign]. Clinvar id is 258121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-58168450-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.72 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLNB	NM_001457.4 linkuse as main transcript	c.7209G>A	p.Ser2403=	synonymous_variant	44/46	ENST00000295956.9	NP_001448.2
FLNB-AS1	NR_135534.1 linkuse as main transcript	n.139+2047C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLNB	ENST00000295956.9 linkuse as main transcript	c.7209G>A	p.Ser2403=	synonymous_variant	44/46	1	NM_001457.4	ENSP00000295956	A1	O75369-1
FLNB-AS1	ENST00000488720.1 linkuse as main transcript	n.140+2047C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0881

AC:

13401

AN:

152134

Hom.:

710

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0618

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.0739

Gnomad ASJ

AF:

0.0585

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0567

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.0606

GnomAD3 exomes

AF:

0.0891

AC:

22390

AN:

251276

Hom.:

1174

AF XY:

0.0878

AC XY:

11926

AN XY:

135822

show subpopulations

Gnomad AFR exome

AF:

0.0598

Gnomad AMR exome

AF:

0.0893

Gnomad ASJ exome

AF:

0.0660

Gnomad EAS exome

AF:

0.000598

Gnomad SAS exome

AF:

0.0653

Gnomad FIN exome

AF:

0.145

Gnomad NFE exome

AF:

0.105

Gnomad OTH exome

AF:

0.0918

GnomAD4 exome

AF:

0.104

AC:

151642

AN:

1459770

Hom.:

8615

Cov.:

AF XY:

0.102

AC XY:

74094

AN XY:

726272

show subpopulations

Gnomad4 AFR exome

AF:

0.0558

Gnomad4 AMR exome

AF:

0.0891

Gnomad4 ASJ exome

AF:

0.0651

Gnomad4 EAS exome

AF:

0.000554

Gnomad4 SAS exome

AF:

0.0669

Gnomad4 FIN exome

AF:

0.146

Gnomad4 NFE exome

AF:

0.112

Gnomad4 OTH exome

AF:

0.0912

GnomAD4 genome

AF:

0.0880

AC:

13395

AN:

152252

Hom.:

708

Cov.:

AF XY:

0.0881

AC XY:

6554

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0616

Gnomad4 AMR

AF:

0.0736

Gnomad4 ASJ

AF:

0.0585

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0566

Gnomad4 FIN

AF:

0.144

Gnomad4 NFE

AF:

0.109

Gnomad4 OTH

AF:

0.0600

Alfa

AF:

0.0995

Hom.:

595

Bravo

AF:

0.0828

Asia WGS

AF:

0.0360

AC:

123

AN:

3478

EpiCase

AF:

0.0948

EpiControl

AF:

0.0925

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

FLNB-Related Spectrum Disorders

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over