rs8640

Positions:

chr3-58168600-C-T

Variant summary

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

The NM_001457.4(FLNB):c.7359C>T(p.Ser2453Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 1,613,232 control chromosomes in the GnomAD database, including 95,127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 12694 hom., cov: 33)

Exomes 𝑓: 0.31 ( 82433 hom. )

Consequence

FLNB
NM_001457.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.06

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 (HGNC:):

FLNB 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=-0.53).

BP6

Variant 3-58168600-C-T is Benign according to our data. Variant chr3-58168600-C-T is described in ClinVar as [Benign]. Clinvar id is 258122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-58168600-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.06 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.891 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.7359C>T	p.Ser2453Ser	synonymous_variant	44/46	ENST00000295956.9	NP_001448.2	O75369-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLNB	ENST00000295956.9 linkuse as main transcript	c.7359C>T	p.Ser2453Ser	synonymous_variant	44/46	1	NM_001457.4	ENSP00000295956.5		O75369-1

Frequencies

GnomAD3 genomes

AF:

0.377

AC:

57258

AN:

151918

Hom.:

12678

Cov.:

show subpopulations

Gnomad AFR

AF:

0.510

Gnomad AMI

AF:

0.367

Gnomad AMR

AF:

0.440

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.913

Gnomad SAS

AF:

0.541

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.352

GnomAD3 exomes

AF:

0.387

AC:

97186

AN:

251398

Hom.:

23757

AF XY:

0.378

AC XY:

51330

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.516

Gnomad AMR exome

AF:

0.527

Gnomad ASJ exome

AF:

0.228

Gnomad EAS exome

AF:

0.918

Gnomad SAS exome

AF:

0.485

Gnomad FIN exome

AF:

0.255

Gnomad NFE exome

AF:

0.256

Gnomad OTH exome

AF:

0.313

GnomAD4 exome

AF:

0.307

AC:

448303

AN:

1461196

Hom.:

82433

Cov.:

AF XY:

0.309

AC XY:

224898

AN XY:

726922

show subpopulations

Gnomad4 AFR exome

AF:

0.522

Gnomad4 AMR exome

AF:

0.513

Gnomad4 ASJ exome

AF:

0.226

Gnomad4 EAS exome

AF:

0.928

Gnomad4 SAS exome

AF:

0.476

Gnomad4 FIN exome

AF:

0.252

Gnomad4 NFE exome

AF:

0.260

Gnomad4 OTH exome

AF:

0.338

GnomAD4 genome

AF:

0.377

AC:

57319

AN:

152036

Hom.:

12694

Cov.:

AF XY:

0.385

AC XY:

28593

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.510

Gnomad4 AMR

AF:

0.441

Gnomad4 ASJ

AF:

0.232

Gnomad4 EAS

AF:

0.913

Gnomad4 SAS

AF:

0.540

Gnomad4 FIN

AF:

0.257

Gnomad4 NFE

AF:

0.257

Gnomad4 OTH

AF:

0.354

Alfa

AF:

0.300

Hom.:

4174

Bravo

AF:

0.396

Asia WGS

AF:

0.719

AC:

2499

AN:

3478

EpiCase

AF:

0.253

EpiControl

AF:

0.259

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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 01, 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. -

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

-0.53

CADD

Benign

1.4

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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